Perceptions in Orthopedic Surgery on the Use of Cannabis in Treating Pain: A Survey of Musculoskeletal Trauma Patients-Results From the Canadian POSIT Study

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“Objectives: To evaluate the patient-reported expectations regarding cannabis for pain following musculoskeletal (MSK) trauma and patients’ perceptions and attitudes regarding its use.

Design: A cross-sectional retrospective survey-based study.

Setting: Three orthopaedic clinics in Ontario (Level-1 trauma center, Level-2 trauma center, rehabilitation clinic).

Patients selection criteria: Adult patients presenting to the clinics from January 24, 2018, to March 7, 2018, with traumatic MSK injuries (fractures/dislocations and muscle/tendon/ligament injury) were administered an anonymous questionnaire on cannabis for MSK pain.

Outcome measures and comparisons: Primary outcome measure was the patients’ perceived effect of cannabis on MSK pain, reported on a continuous pain scale (0%-100%, 0 being no pain, and 100 unbearable pain). Secondary outcomes included preferences, such as administration route, distribution method, timing, and barriers (lack of knowledge, concerns for side effects/addiction, moral/religious opposition, etc.) regarding cannabis use.

Results: In total, 440 patients were included in this study, 217 (49.3%) of whom were female and 222 (50.5%) were male, with a mean age of 45.6 years (range 18-92 years, standard deviations 15.6). Patients estimated that cannabis could treat 56.5% (95% CI 54.0%-59.0%) of their pain and replace 46.2% (95% CI 42.8%-49.6%) of their current analgesics. Nearly one-third (131/430, 30.5%) reported that they had used medical cannabis and more than one-quarter (123/430, 28.6%) used it in the previous year. Most felt that cannabis may be beneficial to treat pain (304/334, 91.0%) and reduce opioid use (293/331, 88.5%). Not considering using cannabis for their injury (132/350, 37.7%) was the most common reason for not discussing cannabis with physicians. Higher reported pain severity (β = 0.2/point, 95% CI 0.1-0.3, P = 0.005) and previous medical cannabis use were associated with higher perceived pain reduction (β = 11.1, 95% CI 5.4-16.8, P < 0.001).

Conclusions: One in 3 orthopaedic trauma patients used medical cannabis. Patients considered cannabis could potentially be an effective option for managing traumatic MSK pain and believed that cannabis could reduce opioid usage following acute musculoskeletal trauma. These data will help inform clinicians discussing medical cannabis usage with orthopaedic trauma patients moving forward.”

https://pubmed.ncbi.nlm.nih.gov/39150305/

https://journals.lww.com/jorthotrauma/abstract/2024/09000/perceptions_in_orthopedic_surgery_on_the_use_of.12.aspx

Integrating Lipidomics, Metabolomics, and Network Pharmacology to Reveal the Mechanism of Cannabidiol against Inflammation in High-Fat, High-Cholesterol Diet-Induced Mice

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“Inflammation plays a critical role in the development of numerous diseases.

Cannabidiol (CBD), found in hemp, exhibits significant pharmacological activities. Accumulating evidence suggests that CBD has anti-inflammatory and cardiovascular protection effects, but the potential mechanisms require further exploration.

In this study, we aimed to reveal the mechanisms of CBD against high-fat, high-cholesterol (HFC) diet-induced inflammation combining metabolomics with network pharmacology.

First, plasma lipidomics results indicated that oxidized lipids could serve as potential biomarkers for HFC diet-induced inflammation, and CBD reversed the elevated levels of oxidized lipids. The HFC diet was also found to enhance intestinal permeability, facilitating the entry of lipopolysaccharides (LPSs) into the circulatory system and subsequently increasing systemic inflammation.

Additionally, cell metabolomic results indicated that CBD could reverse 10 important differential metabolites in LPS-induced RAW 264.7 cells. Using network pharmacology, we identified 49 core targets, and enrichment analysis revealed that arachidonic acid was the most significantly affected by CBD, which was closely associated with inflammation.

Further integrated analysis focused on three key targets, including PTGS2, ALOX5, and ALOX15. Molecular docking showed high affinities between key targets and CBD, and qPCR further demonstrated that CBD could reverse the mRNA expression of these key targets in RAW 264.7 cells.

Collectively, this finding integrates lipidomics and metabolomics with network pharmacology to elucidate the anti-inflammatory effects of CBD and validates key therapeutic targets.”

https://pubmed.ncbi.nlm.nih.gov/39150414/

https://pubs.acs.org/doi/10.1021/acs.jafc.4c04994

CANDI: A Web Server for Predicting Molecular Targets and Pathways of Cannabis-Based Therapeutics

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“Background: Cannabis sativa with a rich history of traditional medicinal use, has garnered significant attention in contemporary research for its potential therapeutic applications in various human diseases, including pain, inflammation, cancer, and osteoarthritis. However, the specific molecular targets and mechanisms underlying the synergistic effects of its diverse phytochemical constituents remain elusive. Understanding these mechanisms is crucial for developing targeted, effective cannabis-based therapies.

Methods: To investigate the molecular targets and pathways involved in the synergistic effects of cannabis compounds, we utilized DRIFT, a deep learning model that leverages attention-based neural networks to predict compound-target interactions. We considered both whole plant extracts and specific plant-based formulations. Predicted targets were then mapped to the Reactome pathway database to identify the biological processes affected. To facilitate the prediction of molecular targets and associated pathways for any user-specified cannabis formulation, we developed CANDI (Cannabis-derived compound Analysis and Network Discovery Interface), a web-based server. This platform offers a user-friendly interface for researchers and drug developers to explore the therapeutic potential of cannabis compounds.

Results: Our analysis using DRIFT and CANDI successfully identified numerous molecular targets of cannabis compounds, many of which are involved in pathways relevant to pain, inflammation, cancer, and other diseases. The CANDI server enables researchers to predict the molecular targets and affected pathways for any specific cannabis formulation, providing valuable insights for developing targeted therapies.

Conclusions: By combining computational approaches with knowledge of traditional cannabis use, we have developed the CANDI server, a tool that allows us to harness the therapeutic potential of cannabis compounds for the effective treatment of various disorders. By bridging traditional pharmaceutical development with cannabis-based medicine, we propose a novel approach for botanical-based treatment modalities.”

https://pubmed.ncbi.nlm.nih.gov/39149470/

https://www.researchsquare.com/article/rs-4744915/v1

The Medicinal Natural Products of Cannabis sativa Linn.: A Review

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“Cannabis sativa is known among many cultures for its medicinal potential. Its complexity contributes to the historical application of various parts of the plant in ethno-medicines and pharmacotherapy. 

C. sativa has been used for the treatment of rheumatism, epilepsy, asthma, skin burns, pain, the management of sexually transmitted diseases, difficulties during child labor, postpartum hemorrhage, and gastrointestinal activity. However, the use of C. sativa is still limited, and it is illegal in most countries. Thus, this review aims to highlight the biological potential of the plant parts, as well as the techniques for the extraction, isolation, and characterization of C. sativa compounds.

The plant produces a unique class of terpenophenolic compounds, called cannabinoids, as well as non-cannabinoid compounds. The exhaustive profiling of bioactive compounds and the chemical characterization and analysis of C. sativa compounds, which modern research has not yet fully achieved, is needed for the consistency, standardization, and the justified application of Cannabis sativa products for therapeutic purposes.

Studies on the clinical relevance and applications of cannabinoids and non-cannabinoid phenols in the prevention and treatment of life-threatening diseases is indeed significant. Furthermore, psychoactive cannabinoids, when chemically standardized and administered under medical supervision, can be the legal answer to the use of C. sativa.”

https://pubmed.ncbi.nlm.nih.gov/35268790/

https://www.mdpi.com/1420-3049/27/5/1689

Medical Cannabis Prescription Practices and Quality of Life in Thai Patients: A Nationwide Prospective Observational Cohort Study

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“Introduction: The legalization of cannabis in Thailand has renewed interest in its traditional medical use. This study aimed to explore the prescribing patterns of traditional practitioners and assess the impact of cannabis oil on patients’ quality of life, with a specific focus on comparing outcomes between cancer and non-cancer patients.

Methods: We conducted a prospective observational cohort study across 30 sites in 21 Thai provinces to analyze the use of “Ganja Oil,” a cannabis extract in 10% coconut oil, prescribed for symptoms like pain, anorexia, and insomnia across a diverse patient group, including cancer and migraines. Quality of life was assessed using the Edmonton Symptom Assessment Scale (ESAS) and EQ-5D-5L at baseline, 1, 2, and 3 months. The study included a predefined subgroup analysis to compare the effects on cancer versus non-cancer patients. Data management was facilitated through Research Electronic Data Capture (REDCap), with statistical analysis performed using Stata/MP.

Results: Among 21,284 participants, the mean age was 54.10 ± 15.32 years, with 52.49% being male. The baseline EQ-5D-5L index was 0.85 ± 0.24. Significant differences in EQ-5D-5L indices were seen between cancer patients (0.79 ± 0.32) and non-cancer patients (0.85 ± 0.23; p < 0.001). ESAS scores also differed significantly between these groups for all symptoms, except anxiety. The most frequent prescription of Ganja Oil was oral administration at bedtime (88.26%), with the predominant dosage being three drops daily, approximately 0.204 mg of tetrahydrocannabinol in total. Posttreatment, significant improvements were noted: the EQ-5D-5L index increased by 0.11 points (95% CI: 0.11, 0.11; p < 0.001) overall, 0.13 points (95% CI: 0.12, 0.14; p < 0.001) for cancer patients, and 0.11 points (95% CI: 0.10, 0.11; p < 0.001) for non-cancer patients. ESAS pain scores improved by -2.66 points (95% CI: -2.71, -2.61; p < 0.001) overall, -2.01 points (95% CI: -2.16, -1.87; p < 0.001) for cancer patients, and -2.75 points (95% CI: -2.80, -2.70; p < 0.001) for non-cancer patients, with similar significant improvements in other symptoms.

Conclusion: Our study indicates potential benefits of Ganja Oil for improving quality of life among Thai patients, as a complementary treatment. These findings must be viewed in light of the study’s design limitations. Further controlled studies are essential to ascertain its efficacy and inform dosing guidelines.”

https://pubmed.ncbi.nlm.nih.gov/39144529/

“This nationwide study marks a substantial step forward in the comprehension of medical cannabis, particularly highlighting its effectiveness in enhancing the quality of life for patients in a real-world setting. It underscores the importance of identifying optimal dosages and the potential benefits of integrating traditional medicine practices with conventional medicine approaches.”

https://karger.com/mca/article/7/1/125/909963/Medical-Cannabis-Prescription-Practices-and

Beneficial Consequences of One-Month Oral Treatment with Cannabis Oil on Cardiac Hypertrophy and the Mitochondrial Pool in Spontaneously Hypertensive Rats

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“Introduction: It has been demonstrated the dysregulation of the cardiac endocannabinoid system in cardiovascular diseases. Thus, the modulation of this system through the administration of phytocannabinoids present in medicinal cannabis oil (CO) emerges as a promising therapeutic approach. Furthermore, phytocannabinoids exhibit potent antioxidant properties, making them highly desirable in the treatment of cardiac pathologies, such as hypertension-induced cardiac hypertrophy (CH). 

Objective: To evaluate the effect of CO treatment on hypertrophy and mitochondrial status in spontaneously hypertensive rat (SHR) hearts. 

Methods: Three-month-old male SHR were randomly assigned to CO or olive oil (vehicle) oral treatment for 1 month. We evaluated cardiac mass and histology, mitochondrial dynamics, membrane potential, area and density, myocardial reactive oxygen species (ROS) production, superoxide dismutase (SOD), and citrate synthase (CS) activity and expression. Data are presented as mean ± SEM (n) and compared by t-test, or two-way ANOVA and Bonferroni post hoc test were used as appropriate. p < 0.05 was considered statistically significant. 

Results: CH was reduced by CO treatment, as indicated by the left ventricular weight/tibia length ratio, left ventricular mass index, myocyte cross-sectional area, and left ventricle collagen volume fraction. The ejection fraction was preserved in the CO-treated group despite the persistence of elevated systolic blood pressure and the reduction in CH. Mitochondrial membrane potential was improved and mitochondrial biogenesis, dynamics, area, and density were all increased by treatment. Moreover, the activity and expression of the CS were enhanced by treatment, whereas ROS production was decreased and the antioxidant activity of SOD increased by CO administration. 

Conclusion: Based on the mentioned results, we propose that 1-month oral treatment with CO is effective to reduce hypertrophy, improve the mitochondrial pool and increase the antioxidant capacity in SHR hearts.”

https://pubmed.ncbi.nlm.nih.gov/39137344/

https://www.liebertpub.com/doi/10.1089/can.2024.0066

Comparative Analysis of Polyphenolic Profile and Chemopreventive Potential of Hemp Sprouts, Leaves, and Flowers of the Sofia Variety

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“This study investigates the phytochemical composition and biological activities of hemp (Cannabis sativa L.) leaves, flowers’ methanolic extracts from the Sofia variety, and its sprouts cultivated under different light conditions (natural light, darkness, blue, and white LED light for 5, 7, and 9 days).

Phytochemical analysis using HPLC identified four key polyphenolic compounds in sprouts’ extracts: chlorogenic, caffeic, and gallic acids, and myricetin, with a predomination of the chlorogenic acid. In contrast, leaves and flowers’ extracts contained cannflavins A and B and chlorogenic, p-coumaric, and ferulic acids, with a significant presence of isochlorogenic acid. Antioxidant capacity, assessed by FRAP method, revealed higher antioxidant potential in leaves compared to flowers and sprouts, with sprouts grown under blue and white LED lights exhibiting the highest activity.

Cytotoxic activity was evaluated on human colon cancer cell lines (HT29, HCT116, DLD-1) and normal colon epithelial cells (CCD 841 CoN).

Results demonstrated significant and selective cytotoxicity against cancer cell lines, with leaves showing more pronounced effects than flowers, and sprouts only moderate activity. All samples revealed an anti-inflammatory effect in vitro.

To conclude, sprouts, leaves, and flowers of the Sofia hemp may be considered promising products for chemoprevention in the future.”

https://pubmed.ncbi.nlm.nih.gov/39124141/

“Cannabis sativa L. is a species of Asian origin that has been cultivated since ancient times for commercial, nutritional, and medicinal purposes.

The results indicate the interesting chemopreventive potential of sprouts, leaves, and flowers from Sofia hemp variety, manifested as cytotoxic, antioxidant, and anti-inflammatory activity.”

https://www.mdpi.com/2223-7747/13/15/2023

Therapeutic Application of Modulators of Endogenous Cannabinoid System in Parkinson’s Disease

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“The endogenous cannabinoid system (ECS) of the brain plays an important role in the molecular pathogenesis of Parkinson’s disease (PD). It is involved in the formation of numerous clinical manifestations of the disease by regulating the level of endogenous cannabinoids and changing the activation of cannabinoid receptors (CBRs). Therefore, ECS modulation with new drugs specifically designed for this purpose may be a promising strategy in the treatment of PD. However, fine regulation of the ECS is quite a complex task due to the functional diversity of CBRs in the basal ganglia and other parts of the central nervous system. In this review, the effects of ECS modulators in various experimental models of PD in vivo and in vitro, as well as in patients with PD, are analyzed. Prospects for the development of new cannabinoid drugs for the treatment of motor and non-motor symptoms in PD are presented.”

https://pubmed.ncbi.nlm.nih.gov/39126088/

“The above indicates the undoubted therapeutic potential of the modulation of the ECS in PD . In recent decades, the ECS has attracted considerable interest as a potential therapeutic target for numerous disorders of the nervous system. Since PD is, clinically, a very polymorphic condition with a variety of motor and non-motor manifestations, it is a useful kind of “model” for assessing the multidimensional action of ECS modulators and is an adequate object for studying the cellular and molecular mechanisms of their action.

Cannabinoids and endocannabinoids hold promise as disease modifiers for the prevention or treatment of neurodegenerative diseases. Experimental and clinical experiences of using ECS modulators in PD and other neurodegenerative diseases create a basis for further intensive therapeutic studies of cannabis and its derivatives in chronic neurodegeneration.”

https://www.mdpi.com/1422-0067/25/15/8520

Development of Delivery Systems with Prebiotic and Neuroprotective Potential of Industrial-Grade Cannabis sativa L

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“This study delves into the transformative effects of supercritical carbon dioxide (scCO2) cannabis extracts and prebiotic substances (dextran, inulin, trehalose) on gut bacteria, coupled with a focus on neuroprotection.

Extracts derived from the Białobrzeska variety of Cannabis sativa, utilising supercritical fluid extraction (SFE), resulted in notable cannabinoid concentrations (cannabidiol (CBD): 6.675 ± 0.166; tetrahydrocannabinol (THC): 0.180 ± 0.006; cannabigerol (CBG): 0.434 ± 0.014; cannabichromene (CBC): 0.490 ± 0.017; cannabinol (CBN): 1.696 ± 0.047 mg/gD). The assessment encompassed antioxidant activity via four in vitro assays and neuroprotective effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The extract boasting the highest cannabinoid content exhibited remarkable antioxidant potential and significant inhibitory activity against both enzymes. Further investigation into prebiotic deliveries revealed their proficiency in fostering the growth of beneficial gut bacteria while maintaining antioxidant and neuroprotective functionalities.

This study sheds light on the active compounds present in the Białobrzeska variety, showcasing their therapeutic potential within prebiotic systems. Notably, the antioxidant, neuroprotective, and prebiotic properties observed underscore the promising therapeutic applications of these extracts.

The results offer valuable insights for potential interventions in antioxidant, neuroprotective, and prebiotic domains. In addition, subsequent analyses of cannabinoid concentrations post-cultivation revealed nuanced changes, emphasising the need for further exploration into the dynamic interactions between cannabinoids and the gut microbiota.”

https://pubmed.ncbi.nlm.nih.gov/39124978/

https://www.mdpi.com/1420-3049/29/15/3574

THC vapor inhalation attenuates hyperalgesia in rats using a chronic inflammatory pain model

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“Humans use cannabinoid drugs to alleviate pain.

As cannabis and cannabinoids are legalized in the U.S. for medicinal and recreational use, it has become critical to determine the potential utilities and harms of cannabinoid drugs in individuals living with chronic pain.

Here, we tested the effects of repeated THC vapor inhalation on thermal nociception and mechanical sensitivity, in adult male and female Wistar rats using a chronic inflammatory pain model (i.e., treated with Complete Freund’s Adjuvant [CFA]).

We report that repeated THC vapor inhalation rescues thermal hyperalgesia in males and females treated with CFA, and also reduces mechanical hypersensitivity in CFA males but not females. Many of the anti-hyperalgesic effects of chronic THC vapor were still observable 24 hours after cessation of the last THC exposure.

We also report plasma levels of THC and its major metabolites, some of which are cannabinoid type-1 receptor (CB1) agonists, after the first and tenth days of THC vapor inhalation. Finally, we report that systemic administration of the CB1 inverse agonist AM251 (1mg/kg; i.p.) blocks the anti-hyperalgesic effects of THC vapor in males and females.

These data provide a foundation for future work that will explore the cells and circuits underlying the anti-hyperalgesic effects of THC vapor inhalation in individuals with chronic inflammatory pain.

PERSPECTIVE: Cannabinoids are thought to have potential utility in the treatment of chronic pain, but few animal studies have tested the effects of chronic THC or cannabis in animal models of chronic pain. We tested the effects of repeated THC vapor inhalation on chronic pain-related outcomes in male and female animals.”

https://pubmed.ncbi.nlm.nih.gov/39121915/

https://www.jpain.org/article/S1526-5900(24)00599-6/abstract