Relief in Gastrointestinal Symptoms with Medical Marijuana Over 1 Year

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“Introduction: Subjective improvement in gastrointestinal (GI) symptoms was assessed among patients using medical marijuana (MMJ).

Methods: Participants completed surveys at 0 days, 30 days, 6 months, and 12 months with questions about the severity of their GI symptoms on a scale from 1 (mild) to 3 (severe).

Results: In each survey, participants reported a significant decrease in GI symptom severity when using MMJ versus when not using MMJ (p < 0.05). The most common self-reported side effects from using MMJ were increased appetite (12-21.4%), fatigue (6-16.7%), anxiety (4-11.9%), cough (4-11.9%), headache (6-7.9%), and dry mouth (4-7.1%).

Conclusion: In patients with chronic GI symptoms, MMJ may provide persistent symptom severity improvement. Limited product availability and mild to moderate side effects are factors to consider before trialing MMJ.”

https://pubmed.ncbi.nlm.nih.gov/39015606/

“Overall, this study suggests there may be a role for MMJ to treat GI symptoms.”

https://karger.com/mca/article/7/1/80/907598/Relief-in-Gastrointestinal-Symptoms-with-Medical

Characteristics for Medical Cannabis Treatment Adherence among Autistic Children and Their Families: A Mixed-Methods Analysis

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“Introduction: Medical cannabis treatment for autistic children has recently become popular, and studies have focused on examining the treatment’s effects on children’s symptom presentation, reported side effects, and dropout rates. However, no previous study has investigated the factors influencing adherence and dropout rates in cannabis treatment.

Method: This explanatory sequential mixed-methods study explored these factors by examining the characteristics of 87 autistic children and their families and deepening parents’ perspectives and experiences of the 6-month CBD-rich cannabis treatment’s benefits and barriers.

Results: We found this treatment to have a high (75%) adherence rate, relatively mild side effects, and substantial reported benefits for the children and families. However, this treatment was not free of barriers; the intake regime, some side effects, and in some cases, unrealistic parental expectations made adherence difficult for some families.

Conclusion: Our results highlight the importance of providing professional guidance and knowledge to parents of autistic children, enhancing their understanding of the impact of CBD-rich cannabis treatment on their children and expected related challenges, and coordinating realistic treatment expectations. We hope that addressing these important aspects will influence parents’ ability to adhere to and enjoy the benefits of cannabis treatment for their autistic children.”

https://pubmed.ncbi.nlm.nih.gov/39015610/

“Our results support the effectiveness of CBD-rich cannabis treatment alongside the importance of professional guidance to inform parents of the treatment’s expected benefits and barriers.”

https://karger.com/mca/article/7/1/68/906156/Characteristics-for-Medical-Cannabis-Treatment

The Relationship between Muscarinic and Cannabinoid Receptors in Neuronal Excitability and Epilepsy: A Review

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“Background: Of the seventy million people who suffer from epilepsy, 40 percent of them become resistant to more than one antiepileptic medication and have a higher chance of death. While the classical definition of epilepsy was due to the imbalance between excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA)-ergic signalling, substantial evidence implicates muscarinic receptors in the regulation of neural excitability.

Summary: Cannabinoids have shown to reduce seizure activity and neuronal excitability in several epileptic models through the activation of muscarinic receptors with drugs which modulate their activity. Cannabinoids also have been effective in reducing antiepileptic activity in pharmaco-resistant individuals; however, the mechanism of its effects in temporal lobe epilepsy is not clear.

Key messages: This review seeks to elucidate the relationship between muscarinic and cannabinoid receptors in epilepsy and neural excitability.”

https://pubmed.ncbi.nlm.nih.gov/39015608/

“Cannabis has been used as a traditional treatment of epilepsy since the 1800s.”

https://karger.com/mca/article/7/1/91/907741/The-Relationship-between-Muscarinic-and

Use and perceptions of Cannabidiol among individuals in treatment for opioid use disorder

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“Background: Cannabidiol (CBD) is a widely available cannabis product with many claims as to potential health benefits including alleviating symptoms related to opioid use disorder (OUD). However, little is known as to how individuals with OUD perceive CBD, to what extent they may already be using CBD, and for what purposes.

Methods: A survey was conducted among individuals receiving treatment for OUD at the Addiction Institute of Mount Sinai in New York City from July 2021 to August 2023. The survey consisted of demographic questions, questions about opioid use, CBD use, and perceptions regarding CBD. Statistical analysis using ordinal logistic regression was employed to compare perceptions between CBD users and non-users while adjusting for age and race.

Results: Among 587 respondents, 550 completed the survey. Among all survey completers, 129 (23%) reported a history of using CBD for a variety of reasons including: anxiety (81, 62.8%), pain (65, 50.4%), sleep (63, 48.8%), depression (62, 48.1%), recreational purposes (32, 24.8%), or for other reasons (8, 6.2%). Of note, 22 (17.1%) respondents reported using CBD to control their addiction and 54 (41.9%) reported using CBD to ease opioid withdrawal symptoms. CBD users demonstrated more positive perceptions regarding its legality (β = 0.673, OR = 1.960, 95% CI [1.211, 3.176], p = .006), social acceptance (β = 0.718, OR = 2.051, 95% CI [1.257, 3.341], p = .004), and therapeutic potential compared to non-users. CBD users also had a more positive view of its potential future role in managing addiction (β = 0.613, OR = 1.846, 95% CI [1.181, 2.887], p = .007).

Conclusions: This study highlights a significant association between CBD usage and progressive views regarding CBD among individuals with OUD, suggesting a growing interest in CBD as a potential adjunctive therapy for individuals in substance use treatment. Some patients are already using CBD for anxiety, pain, sleep, depression, or as a harm reduction intervention to control their addiction or for opioid withdrawal symptoms. These findings underscore the importance of integrating patient perspectives into future research and treatment strategies involving CBD in the context of OUD.”

https://pubmed.ncbi.nlm.nih.gov/39020418/

“The current survey study provides valuable insights into the usage and perceptions of CBD among individuals in treatment for OUD. The findings reveal that some patients are already using CBD for a variety of reasons including anxiety, pain, sleep, depression, or as a harm reduction intervention to control their opioid use or minimize opioid withdrawal symptoms. This is often done without the knowledge of their healthcare providers. Respondents overall had a positive view of CBD suggesting a growing interest in its use as a potential adjunctive therapy for individuals with substance use disorders. The results also emphasize the importance of incorporating patient real-world experience and opinions into the development of future research and treatment approaches. By doing so, we can create more effective, patient-centered strategies that address the complexities of the opioid overdose crisis. Robust clinical research and clear medical guidelines are essential to harness the full potential of CBD as a harm reduction tool, ultimately improving outcomes for those struggling with OUD.”

https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-024-01051-5

Cannabidiol ameliorates lipopolysaccharide-induced cardiovascular toxicity by its antioxidant and anti-inflammatory activity via regulating IL-6, Hif1α, STAT3, eNOS pathway

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“Background: Systemic inflammation causes several organ damage by activating the intracellular signaling mechanisms. Heart and aorta tissues are the structures mostly affected by this situation. By examining underlying processes, this study sought to determine whether cannabidiol (CBD) may have protective effects against the cardiovascular damage brought on by lipopolysaccharide (LPS).

Materials and methods: A total of 32 female rats were randomly allocated to one of four groups: control, lipopolysaccharide (LPS) (5 mg/kg, i.p., single dose), LPS + CBD (5 mg/kg, i.p., single dose), and CBD groups. The rats were killed six hours after receiving LPS, and tissues from the heart and aorta were taken. Histopathological and immunohistochemical analyzes were performed. Oxidative stress was evaluated biochemically by spectrophotometric method. Expression levels of genes were studied by RT-qPCR method.

Results: Histopathological analysis of the LPS group showed moderate hyperemia, hemorrhages, edema, inflammation, and myocardial cell damage. There was a slight to moderate increase in Cox-1, G-CSF, and IL-3 immunoexpressions, along with enhanced expressions of IL-6, Hif1α, and STAT3 genes, and decreased expressions of eNOS genes. Additionally, there were increased levels of TOS and decreased TAS levels observed biochemically. CBD treatment effectively reversed and improved all of these observed changes.

Conclusions: CBD protects the heart and aorta against systemic inflammation through its antioxidant and anti-inflammatory activity via regulating IL-6, Hif1α, STAT3, and eNOS intracellular pathways.”

https://pubmed.ncbi.nlm.nih.gov/39023749/

https://link.springer.com/article/10.1007/s11033-024-09772-3

High cannabigerol hemp extract moderates colitis and modulates the microbiome in an inflammatory bowel disease model

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“Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease.

In this study, we utilize the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, non-euphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control.

Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota, that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation.

Taken together these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. 

Significance Statement Using the DSS model of colitis, we show that treatment with high CBG hemp extract reduces the severity of symptoms associated with colitis. Additionally, we show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.”

https://pubmed.ncbi.nlm.nih.gov/39009468/

https://jpet.aspetjournals.org/content/early/2024/07/15/jpet.124.002204

Synthesis and antiproliferative activity of CBD aromatic ester derivatives

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“This study involved the synthesis of a series of novel cannabidiol (CBD) aromatic ester derivatives, including CBD-8,12-diaromaticester derivatives (compounds 2a-2t) and CBD-8,12-diacetyl-21-aromaticester derivatives (compound 5a-5c).

The antiproliferative activities of these compounds against human liver cancer cell lines HePG2 and HeP3B as well as human pancreatic cancer cell lines ASPC-1 and BXPC-3 were evaluated in vitro using the CCK-8 assay.

The results indicated that compound 2f exhibited an IC50 value of 2.75 µM against HePG2, which is 5.32-fold higher than that of CBD. Additionally, compounds 2b and 5b demonstrated varying degrees of improved anticancer activity (IC50 5.95-9.21 µM) against HePG2.”

https://pubmed.ncbi.nlm.nih.gov/39004890/

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2369914

Cutaneous Wound Healing and the Effects of Cannabidiol

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“Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries.

To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems.

The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM).

The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds.

CBD may have some beneficial effects in diabetic wounds. We applied 6-mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD.

These data support the potential use of CBD to improve diabetic cutaneous wound healing.”

https://pubmed.ncbi.nlm.nih.gov/39000244/

“The endocannabinoid system is an elaborate, complex, and adaptive monitoring and modulating apparatus. Phytocannabinoids mimic the actions of the endogenous bioactive lipids derived from arachidonic acid and have unequivocal and very wide-ranging effects, including decreasing inflammatory responses following cutaneous injuries. While we will continue to explore, at the macroscopic level, the therapeutic clinical applications, the efforts to understand mechanistically, at the micro- and nano-levels, why and how CBD causes these observed beneficial effects are increasingly more important. Such a multi- or trans-scalar (fractal) approach allows for the targeted expansion and refinement of CBD use.”

https://www.mdpi.com/1422-0067/25/13/7137

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis

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“Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making.

Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis.

Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20.

Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.”

https://pubmed.ncbi.nlm.nih.gov/38994494/

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1243597/full

Impact of Medical Cannabis on Recovery from Playing-Related Musculoskeletal Disorders in Musicians: An Observational Cohort Study

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“Introduction: Playing-related musculoskeletal disorders (PRMDs) are musculoskeletal symptoms that interfere with the ability to play at the level a musician is accustomed to. Musicians have an 84% lifetime prevalence of PRMD. Many types of analgesia are inappropriate for this population due to their risks, but cannabidiol (CBD) has been shown to have anti-inflammatory properties and can reduce the perception of pain. Medical cannabis has also been shown to be safer than other analgesia in terms of serious adverse events. This study explores the impact of medical cannabis for PRMD on perceptions of pain and mental health outcomes.

Methods: Participants (n = 204) completed questionnaires at baseline and six months: the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM) and Depression, Anxiety and Stress Scale (DASS-21). Participants self-selected their group: non-cannabis users (n = 42), new medical cannabis users (n = 61), and long-term medical cannabis users (n = 101). Data were analyzed using paired t-tests for within-group and ANOVA for between-group differences.

Results: At six months, there was no difference (p = 0.579) in cannabidiol dose between new (24.87 ± 12.86 mg) and long-term users (21.48 ± 12.50 mg). There was a difference in tetrahydrocannabinol (THC) dose (p = 0.003) between new (3.74 ± 4.22 mg) and long-term users (4.41 ± 5.18 mg). At six months, new cannabis users had a significant reduction in pain intensity as measured by The Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM40) (p = 0.002). Non-users (p = 0.035), new users (p = 0.002), and long-term cannabis users (p = 0.009) all had significant reductions in pain interference (MPIIQM50) at six months. At six months, non-cannabis (p = 0.022) and long-term cannabis users (p = 0.001) had an improvement in DASS-21. The change in pain intensity was the only difference between groups, F(2, 201) = 3.845, p = 0.023. This difference was between long-term (0.83 ± 0.79) and new users (-2.61 ± 7.15). No serious adverse events occurred, and a minority experienced tiredness, cough, and dry mouth.

Discussion/conclusions: This practice-based evidence demonstrated that the multidimensional approach to care provided by the Musicians’ Clinics of Canada benefited all groups at six months. Medical cannabis significantly reduced pain intensity in new users of medical cannabis with PRMD, and all groups saw improvements in pain interference. In keeping with prior studies, medical cannabis seems to be effective at reducing perceptions of pain, including for PRMD. CBD/THC dosing was within guideline recommendations, and no patients experienced any serious adverse events. Limitations include multiple factors impacting patients’ decisions to opt in or out of medical cannabis. These include cost, comorbidities, and disease chronicity. In conclusion, medical cannabis reduces pain intensity in new users, and when combined with a multidimensional approach to care, patients with PRMD can see improvements in pain as well as mental wellbeing.”

https://pubmed.ncbi.nlm.nih.gov/38998869/

“In conclusion, within our study population over a six-month period, medical cannabis proved to be a safe and potentially beneficial treatment option for musicians with PRMD, with those using medical cannabis for the first time seeing a statistically significant reduction in pain intensity. All patient groups experienced an improvement in some domains of pain experience or mental wellbeing, likely due to the multidimensional model of care. Many patient concerns about medical cannabis include adverse drug effects, addiction, tolerance, losing control, or unusual behavior [21], but hopefully this paper will add further evidence to the literature to help patients make informed decisions in keeping with their preferences and values. A key conclusion from this study is the importance of shared decision making to ensure that patient values, as well as individual symptoms and situations, are considered. N-of-1 trials may be used to further explore optimal individualized treatment plans [49], as well as randomized-controlled trials to build the evidence base for musicians with PRMD in general.”

https://www.mdpi.com/2227-9032/12/13/1335