“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.”
“Objectives: Billions of individuals worldwide suffer from periodontal disease, an inflammatory disease that results in hard-tissue and soft-tissue destruction. A viable therapeutic option to treat periodontal disease may be via cannabinoids that exert immunomodulatory effects, and the endocannabinoid system (ECS) is readily present in periodontal tissues that exhibit cannabinoid type 1 and 2 receptors (CB1R and CB2R). Phytocannabinoids (pCBs), which are a part of a heterogeneous group of molecules acting on cannabinoid receptors (CBR) derived from the cannabis plants, have been attributed to a wide variety of effects including anti-inflammatory activity and some pro-inflammatory effects depending on the cell type. Thus, this study aims to examine the effects of pCBs on primary human gingival fibroblasts (HGFs) in IL-1β stimulated (simulated periodontal disease) HGFs.
Results: Cannabidivarin (CBVN or CBDV) (EC50 = 12 nM) and cannabigerol (CBG) (EC50 = 30 nM) exhibited agonist activity on CB2R with intermediate efficacy. Cannabidiol (CBD) did not exhibit activation of the CB2R, and the CB1R activation was not observed with any of the pCBs. Cytotoxicity results showed that concentrations of 2.50 μg/ml or greater for the pCBs were toxic except for CBVN. Lower concentrations of CBD and CBG (0.1-0.75 μg/ml), and CBVN at 2.50 μg/ml exhibited significant effects on HGF proliferation. In IL-1β-stimulated HGFs, prostaglandin E2 (PGE2) production was significantly suppressed only by CBG and CBVN. CBD and CBG treatment alone did, however, elevate PGE2 production significantly compared to control. IL-1β stimulation resulted in a robust increase in the production of all cytokines tested. Treatment of IL-β-stimulated HGF with the three pCBs (1 μg/ml) significantly reduced INF-ɣ, TNF-α, and IL-2. The significant suppression of IL-4 was seen with CBD and CBVN, while only CBVN exerted suppression of IL-13. The three pCBs significantly increased IL-6, IL-10, and IL-12 levels, while none of the pCBs reduced the expression of IL-8 in IL-1β-stimulated HGF.
Conclusion: The effective inhibition of IL-1β-stimulated production of PGE2 and cytokines by the pCB in HGFs suggests that targeting the endocannabinoid system may lead to the development of therapeutic strategies for periodontal therapy. However, each pCB has its unique anti-inflammatory profile, in which certain pro-inflammatory activities are also exhibited. The pCBs alone or in combination may benefit and aid in improving public oral health.”
“Cannabis sativa L. has been known for at least 2000 years as a source of important, medically significant specialised metabolites and several bio-active molecules have been enriched from multiple chemotypes. However, due to the many levels of complexity in both the commercial cultivation of cannabis and extraction of its specialised metabolites, several heterologous production approaches are being pursued in parallel.
In this review, we outline the recent achievements in engineering strategies used for heterologous production of cannabinoids, terpenes and flavonoids along with their strength and weakness. We provide an overview of the specialised metabolism pathway in C. sativa and a comprehensive list of the specialised metabolites produced along with their medicinal significance.
We highlight cannabinoid-like molecules produced by other species. We discuss the key biosynthetic enzymes and their heterologous production using various hosts such as microbial and eukaryotic systems. A brief discussion on complementary production strategies using co-culturing and cell-free systems is described. Various approaches to optimise specialised metabolite production through co-expression, enzyme engineering and pathway engineering are discussed. We derive insights from recent advances in metabolic engineering of hosts with improved precursor supply and suggest their application for the production of C. sativa speciality metabolites.
We present a collation of non-conventional hosts with speciality traits that can improve the feasibility of commercial heterologous production of cannabis-based specialised metabolites. We provide a perspective of emerging research in synthetic biology, allied analytical techniques and plant heterologous platforms as focus areas for heterologous production of cannabis specialised metabolites in the future.”
“Introduction: Amotivational syndrome is a term used to refer to lack of motivation and passive personality related to chronic cannabis use. Given mixed findings, the current study aimed to replicate and extend previous research on frequent cannabis use, motivated behavior, and self-reported apathy.
Method: Cannabis users (on average, ≥3 days/week of cannabis use over the past year), and healthy controls (≤1 day/month of cannabis use over the past year) completed the Apathy Evaluation Scale (AES), and the Effort Expenditure for Rewards Task (EEfRT). Repeated measures analysis of covariance was used to 1) examine the effects of group, reward magnitude, probability, and their interaction on hard task selections on the EEfRT, and 2) examine between-group differences on the AES, controlling for alcohol use and depressive symptoms.
Results: There were significant main effects of reward magnitude, probability, and an interaction between reward magnitude and probability on hard task selection (p‘s < 0.05). Specifically, as reward magnitude and probability of winning the reward increased, participants were more likely to select hard tasks on the EEfRT. Relative to healthy controls, cannabis users were significantly more likely to select hard tasks on the EEfRT (F(1,56) = 6.49, p = 0.014, ηp2= 0.10). When controlling for alcohol use and depressive symptoms, no significant group differences in self-reported apathy were present (p = 0.46).
Conclusions: Cannabis users exhibit a greater likelihood of exerting more effort for reward, suggesting enhanced motivation relative to healthy controls. Thus, the current results do not support amotivational syndrome in adult frequent cannabis users. Despite some harms of long-term cannabis use, amotivation may not be among them.”
“Effort-related decision making and cannabis use among college students. The results provide preliminary evidence suggesting that college students who use cannabis are more likely to expend effort to obtain reward, even after controlling for the magnitude of the reward and the probability of reward receipt. Thus, these results do not support the amotivational syndrome hypothesis.”
“Background: Cannabis use may be linked with anhedonia and apathy. However, previous studies have shown mixed results and few have examined the association between cannabis use and specific reward sub-processes. Adolescents may be more vulnerable to harmful effects of cannabis than adults. This study investigated (1) the association between non-acute cannabis use and apathy, anhedonia, pleasure, and effort-based decision-making for reward, and (2) whether these relationships were moderated by age-group.
Methods: We used data from the ‘CannTeen’ study. Participants were 274 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 days/week use in the past three months), and gender- and age-matched controls. Anhedonia was measured with the Snaith-Hamilton Pleasure Scale (n=274), and apathy was measured with the Apathy Evaluation Scale (n=215). Effort-based decision-making for reward was measured with the Physical Effort task (n=139), and subjective wanting and liking of rewards was measured with the novel Real Reward Pleasure task (n=137).
Results: Controls had higher levels of anhedonia than cannabis users (F1,258=5.35, p=.02, ηp2=.02). There were no other significant effects of User-Group and no significant User-Group*Age-Group interactions. Null findings were supported by post hoc Bayesian analyses.
Conclusion: Our results suggest that cannabis use at a frequency of three to four days per week is not associated with apathy, effort-based decision-making for reward, reward wanting, or reward liking in adults or adolescents. Cannabis users had lower anhedonia than controls, albeit at a small effect size. These findings are not consistent with the hypothesis that non-acute cannabis use is associated with amotivation.”
“Legalization of cannabis by U.S. states is likely increasing the use of cannabis as an alternative to conventional pharmaceutical drugs. We examined how cannabis legalization between 1996 and 2019 affected stock market returns for listed generic and brand pharmaceutical companies and found that returns were 1.5-2% lower at 10 days after legalization. Returns decreased in response to both medical and recreational legalization, for both generic and brand drugmakers. Investors anticipate a single legalization event to reduce drugmaker annual sales by $3B on average.”
“Using a data set and estimation approach novel to health policy, we find evidence that investors predict legal cannabis access will significantly decrease sales of conventional pharmaceutical drugs. Legal cannabis applies competitive pressure to both generic and brand drug markets, across both classes of drugmakers. This makes legal cannabis distinct from typical brand drug patent expiration and generic drug entry where typically only one drug, the drug coming off patent, and its substitutes are affected. Furthermore, cannabis can be purchased without a prescription and home cultivated, unlike any other conventional medication.”
“The excessive consumption of ultra-processed foods and the development of obesity has been associated with several comorbidities, including psychiatric disorders. Excess fat tissue promotes a low-intensity inflammatory state, mainly in the white tissue, which is essential in developing metabolic alterations and influences brain homeostasis.
In this scenario, Cannabidiol (CBD), a compound from Cannabis sativa, has presented anxiolytic and anti-inflammatory effects in murine models.
This study verified whether CBD treatment would ameliorate the compulsive-like and anxiety-like behaviors observed after mice’s chronic consumption of a high-refined carbohydrate (HC) diet.
BALB/c male mice received a control or HC diet for 12 weeks followed by vehicle and CBD (30 mg/Kg, i.p.) administration, and their behavior was evaluated in the Marble Burying test (MB) and Novel Suppressing Feeding test (NSF).
The sub-chronic, but not acute, treatment with CBD attenuated the compulsive-like and anxiogenic-like behavior induced by the HC diet.
Our data reinforced the harmful effects of the HC diet’s chronic consumption on compulsive and anxious behaviors and the potential of CBD as a drug treatment for psychiatric disorders associated with obesity.”
“Objectives: Medical marijuana is a symptom treatment option for palliative cancer patients; however, its useful applications remain limited. The goals of this study were to review the characteristics of patients who received medical marijuana under our ambulatory palliative care program and to determine barriers to access and use of medical marijuana in this population.
Methods: This study was a retrospective analysis of patients who were enrolled in the medical marijuana registry through the ambulatory palliative care department at Upstate Cancer Center. Data from June 2017 to June 2020 were analyzed. Patients were included if they had a diagnosis of cancer, were certified by a qualified practitioner in the New York Medical Marijuana Program, and received care at Upstate Medical University. Patients were excluded if no marijuana certificate was found or if they transferred care.
Results: The study population was 184 patients. Ninety-three patients (51.5%) received at least one prescription from a New York licensed marijuana dispensary while 72 (39.13%) were certified but never obtained any medical marijuana. For patients who took at least one dose of medical marijuana, 48.14% experienced an improvement in pain, 44.95% used fewer opioids, and 85.11% had an improvement in at least one symptom. Adverse effects were low at 3.72%.
Conclusion: Medical marijuana has an important role in the palliation of symptoms in advanced cancers with few adverse effects. There are still many barriers to effective use. More prospective research is needed to optimize delivery and dosing.”
“Medical marijuana appears to have an important role in the palliation of symptoms in advanced cancers with few adverse effects although not all patients certified for use, go on to obtain it. There are many remaining barriers to effective use including financial toxicity and end-of-life care, introducing this so late in life that the benefit is limited.”
