“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.”
“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.”
“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.”
“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.”
“Purpose of review: There have been many debates, discussions, and published writings about the therapeutic value of cannabis plant and the hundreds of cannabinoids it contains. Many states and countries have attempted, are attempting, or have already passed bills to allow legal use of cannabinoids, especially cannabidiol (CBD), as medicines to treat a wide range of clinical conditions without having been approved by a regulatory body. Therefore, by using PubMed and Google Scholar databases, we have reviewed published papers during the past 30 years on cannabinoids as medicines and comment on whether there is sufficient clinical evidence from well-designed clinical studies and trials to support the use of CBD or any other cannabinoids as medicines.
Recent findings: Current research shows that CBD and other cannabinoids currently are not ready for formal indications as medicines to treat a wide range of clinical conditions as promoted except for several exceptions including limited use of CBD for treating two rare forms of epilepsy in young children and CBD in combination with THC for treating multiple-sclerosis-associated spasticity.
Summary: Research indicates that CBD and several other cannabinoids have potential to treat multiple clinical conditions, but more preclinical, and clinical studies and clinical trials, which follow regulatory guidelines, are needed to formally recommend CBD and other cannabinoids as medicines.”
“Based on preliminary preclinical and clinical research, cannabinoids could be further investigated for their potential in treating a wide range of clinical conditions. For their effects on neuroinflammation, inflammatory cytokines, psychosis, fibrosis, and immunomodulation, many of these cannabinoids may be further investigated for treating clinical indications ranging from seizures/epilepsy in adults, schizophrenia, obesity, nausea, neuropathy, retinopathy nephropathy, pain, and dermal conditions like dermatitis and acne.”
“Cannabis has been used in even the oldest traditional medicines available. In the last century, negative attention has prevailed regarding the psychotropic and abuse potential. For this reason, Cannabis has been banned and declared illegal in many countries. In recent years, however, there has been a more in-depth evaluation of the legalization of cannabinoids for medical use in several countries following heightened media attention and reports of effectiveness, although not always thoroughly backed up by scientific evidence. The official introduction of pharmaceutical-grade Cannabis inflorescences for medicinal purposes has allowed physicians and pharmacists, to prescribe and prepare several Cannabis preparations legally. Such products are currently being administered to patients without their efficacy being evaluated in controlled studies: for each patient the composition and route of administration may differ. In addition, many advanced administration systems have been developed or are still under development, but few clinical trials have been completed.
In this context, this Research Topic focused on the in-depth analysis of the legal, technological and pharmacological aspects related to the medical use of Cannabis-based formulations.
Anil et al. have directed their research specifically on the activity of Cannabis for medical use in the context of inflammatory processes. Although activities in this area are plausible, the high number of active molecules produced by Cannabis and simultaneously administered through the extractive products normally used in therapy, has not yet made it possible to identify their specific mechanisms of action. Once the modalities of action of the active molecules have been clarified, it might be of interest to use purified mixtures to obtain a more significant activity potentially (Anil et al.).
Specific literature reviews were then done for some pathologies such as when Xin et al. investigated the potential therapeutic effect of CBD in bone diseases. Even in this case, further studies are needed to evaluate the benefits and risks of cannabinoids’ use (Xin et al.).
A large part of the clinical research relating to Cannabis for medical use concerns its use in the context of diseases of the central nervous system. Ortiz et al. examined evidence supporting the therapeutic utility of cannabinoids for treating neurodegenerative diseases, pain, mood disorders, and substance use disorders. Important considerations were also made on the methods of formulation and the routes of administration (Ortiz et al.). Lacroix et al. Also considered Cannabis in neurological disorders stressing that currently most of the scientific data supports the potential therapeutic use of Cannabis but, as much as patients request it, the knowledge is still too little in-depth. It is therefore certainly urgent to manage clinical trials to provide stronger and safer evidence (Lacroix et al.).
Procaccia et al. discussed how phytocannabinoid profiles differed between plants according to chemovar types and examined the main factors influencing the accumulation of secondary metabolites in the plant, including genotype, growing conditions, processing, storage and the delivery route; the authors highlighted how these factors make the use of Cannabis in therapy highly complex (Procaccia et al.).
In addition to the more well-known compounds such as THC and CBD, Cannabis produces over 120 other phytocannabinoids. The use of THC is associated with acute psychotropic effects that could potentially be avoided considering that minor cannabinoids and their chemical counterparts could offer the same potential benefits without the same adverse effects. In this regard, Walsh et al. reviewed the literature to provide an overview of the endocannabinoid system, phytocannabinoid biosynthesis and a discussion on molecular pharmacology. Potential therapeutic uses of minor cannabinoids underlining that future studies will have to rigorously evaluate these compounds’ risk/benefit ratio (Walsh et al.).
The interest in molecules other than cannabinoids such as terpenes is certainly relevant. This interest has grown even greater since the possibility of an “entourage” effect between the active molecules of Cannabis has been postulated. Accordingly, Finlay et al. in their study examined whether some terpenes acted directly on cannabinoid receptors. From the results obtained, it was not possible to exclude the existence of an entourage effect. Still, this cannot be linked to a direct action of the terpenes on the cannabinoid receptors. However, the pharmacological mechanism underlying this substances activity remains to be thoroughly investigated (Finlay et al.).
Maayah et al. pointed out that full-spectrum Cannabis extracts have been used in clinical trials to treat various diseases. However, despite their efficacy, their potential use in therapy may be limited by possible behavioural side effects. These researchers then successfully worked on experimental animals to identify a panel of blood metabolites predicting behavioural effects (Maayah et al.).
Pennypacker et al. have evaluated whether the products available on the market in the United States of America are consistent in the concentration of cannabinoids, with the literature indications for use in therapy. Overall, the results of this study have been defined by the authors as alarming as current product offerings do not reflect scientific evidence (Pennypacker et al.).
In the regulatory context MacPhail et al. have analysed the trend of prescriptions in Australia over the last 5 years, noting a substantial increase in prescriptions over time that does not actually reflect a worsening of the pathological conditions of the population but rather a greater prescription linked to greater knowledge and acceptance of this type of therapy (MacPhail et al.).
As regards the use in therapy of medical Cannabis, the current regulations have been analysed by Baratta et al. in those countries where clinical studies have recently been conducted. The results of the trials have been crossed with the pathologies for which the current legislation provides that it is possible to prescribe Cannabis allowing relevant considerations (Baratta et al.).
From all the publications collected, it is clear that there is a great interest in the enormous potential of Cannabis in the medical field but also a widespread awareness of the extreme need to conduct in-depth research that clarifies the mechanisms of action of the quantity of components present in the phytocomplex of this plant species.”
“Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence. Indeed, the peripherally-restricted CB1R specific antagonist AM6545 showed significant mnemonic effects that were occluded in adrenalectomized mice, and after peripheral adrenergic blockade. AM6545 also transiently impaired contextual fear memory extinction. Vagus nerve chemogenetic inhibition reduced AM6545-induced mnemonic effect. Genetic CB1R deletion in dopamine β-hydroxylase-expressing cells enhanced recognition memory persistence. These observations support a role of peripheral CB1R modulating adrenergic tone relevant for cognition. Furthermore, AM6545 acutely improved brain connectivity and enhanced extracellular hippocampal norepinephrine. In agreement, intra-hippocampal β-adrenergic blockade prevented AM6545 mnemonic effects. Altogether, we disclose a novel CB1R-dependent peripheral mechanism with implications relevant for lengthening the duration of non-emotional memory.”
“The endocannabinoid system is located throughout the central and peripheral nervous systems, endocrine system, gastrointestinal system, and within inflammatory cells. The use of medical cannabinoids has been gaining traction as a viable treatment option for varying illnesses in recent years. Research is ongoing looking at the effect of cannabinoids for treatment of common otolaryngologic pathologies. This article identifies common otolaryngologic pathologies where cannabinoids may have benefit, discusses potential drawbacks to cannabinoid use, and suggests future directions for research in the application of medical cannabinoids.”
“Background: Recent studies suggested that individuals with metabolic disorders have altered function of adipocytes and adipose stem cell subpopulations, which impairs tissue homeostasis, promoting insulin resistance and diabetes development. The non-psychoactive phytocannabinoid CBD was found to modulate adipose tissue metabolism, however, its exact role in controlling ASCs’ fate is still poorly understood.
Objectives: This investigation aimed to elucidate whether pretreatment of ASCs with CBD can protect against ER stress development and maintain the cytophysiological properties of cells.
Methods: Human ASCs were cultured under control and adipogenic conditions. Prior to the experiments, cells in the experimental group were pretreated with CBD following the addition of an ER stress inducer-tunicamycin. After the experiments, the cells were subsequently tested for expression of the apoptotic, ER stress, and anti-inflammatory-related genes using RT-qPCR. Oxidative stress was analysed with flow cytometric assays.
Results: Cells pretreated with CBD displayed decreased apoptosis and enhanced proliferation rate. Additionally, the expression of pro-inflammatory cytokines and miRNAs was significantly reduced. The obtained results also demonstrated an obvious reduction in intracellular accumulated ROS and NO, as well as mitigated ER stress through the down-regulation of IRE-1, PERK, CHOP, and ATF6 transcripts upon CBD treatment.
Conclusion: The presented data provide the evidence that CBD protects ASCs against ER stress development and its complications and, thus, offers new insights for the management of obesity through the regulation of adipose tissue dynamics.”
“The regenerative potential of ASCs in the treatment of multiple disorders lies in their differentiation, migration, and secretory activity. However, these conditions impair the cytophysiological properties of ASCs, limiting their application in autologous therapies. What is more, impaired ASCs in vivo suffer from reduced multipotency and produce a vast number of inflammatory cytokines and oxidative stress factors, which in turn contributes to disease progression. Hence, development of strategies that reverse their senescence and ageing, and, as a consequence, restore regenerative properties are strongly desirable.
To our knowledge, this is the first report on the impact of CBD pretreatment on metabolically impaired ASCs suffering from ER stress. Our current study revealed that CBD modulates ASCs metabolism by promoting their growth kinetics, multipotency, and viability, which due to enhanced ER stress were strongly limited. Taking into account that CBD lacks psychopharmacological activity, further studies aiming at unravelling its influence on different stem cells populations are recommended and justified. Further studies on the effects of CBD on ASCs could explore other measures of its regenerative capacity than studied in the presented research. Furthermore, unravelling the precise molecular mechanisms of action via CBD that protect ASCs against cytophysiological impairment would be valuable. While our findings are supported by the existing literature, our research was not free of limitations. An important drawback is that we did not explore which cannabinoid receptors are responsible for the observed effects of CBD. Thus, further experiments utilizing agonists and antagonists of cannabinoid receptors are necessary to elucidate which of them are involved in CBD’s way of action.
Taking into consideration that ASCs are nowadays a commonly applied tool in regenerative medicine, the ability to enhance their stemness and regenerative potential may contribute not only to more effective therapies but also to significantly reducing the costs associated with their isolation and expansion.”
“Background: Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB2 and serotonin 5HT1A receptors included. These two receptors may interact to form heteromers (CB2-5HT1A-Hets) that are also a target of CBD.
Aims: We aimed to assess whether the expression and function of CB2-5HT1A-Hets is affected by CBD in animal models of hypoxia of the neonate and in glucose- and oxygen-deprived neurons.
Methods: We developed a quantitation of signal transduction events in a heterologous system and in glucose/oxygen-deprived neurons. The expression of receptors was assessed by immuno-cyto and -histochemistry and, also, by using the only existing technique to visualize CB2-5HT1A-Hets fixed cultured cells and tissue sections (in situ proximity ligation PLA assay).
Results: CBD and cannabigerol, which were used for comparative purposes, affected the structure of the heteromer, but in a qualitatively different way; CBD but not CBG increased the affinity of the CB2 and 5HT1A receptor-receptor interaction. Both cannabinoids regulated the effects of CB2 and 5HT1A receptor agonists. CBD was able to revert the upregulation of heteromers occurring when neurons were deprived of oxygen and glucose. CBD significantly reduced the increased expression of the CB2-5HT1A-Het in glucose/oxygen-deprived neurons. Importantly, in brain sections of a hypoxia/ischemia animal model, administration of CBD led to a significant reduction in the expression of CB2-5HT1A-Hets.
Conclusions: Benefits of CBD in the hypoxia of the neonate are mediated by acting on CB2-5HT1A-Hets and by reducing the aberrant expression of the receptor-receptor complex in hypoxic-ischemic conditions. These results reinforce the potential of CBD for the therapy of the hypoxia of the neonate.”
