The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® – A Cannabis-derived Spray

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“Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants.

Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders.

The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.”

https://pubmed.ncbi.nlm.nih.gov/38318827/

https://www.eurekaselect.com/article/138318

Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression

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“Introduction: Thermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes.

Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure.

Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds.

Methods: Deep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α).

Results: Topical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed.

Conclusions: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.”

https://pubmed.ncbi.nlm.nih.gov/38320364/

https://www.journalofsurgicalresearch.com/article/S0022-4804(24)00037-4/fulltext

Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-β and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment

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“Introduction: Cannabis sativa is utilized mainly for palliative care worldwide. Ovarian cancer (OC) is a lethal gynecologic cancer. A particular cannabis extract fraction (‘F7’) and the Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor niraparib act synergistically to promote OC cell apoptosis. Here we identified genetic pathways that are altered by the synergistic treatment in OC cell lines Caov3 and OVCAR3. 

Materials and methods: Gene expression profiles were determined by RNA sequencing and quantitative PCR. Microscopy was used to determine actin arrangement, a scratch assay to determine cell migration and flow cytometry to determine apoptosis, cell cycle and aldehyde dehydrogenase (ALDH) activity. Western blotting was used to determine protein levels. 

Results: Gene expression results suggested variations in gene expression between the two cell lines examined. Multiple genetic pathways, including Hippo/Wnt, TGF-β/Activin and MAPK were enriched with genes differentially expressed by niraparib and/or F7 treatments in both cell lines. Niraparib + F7 treatment led to cell cycle arrest and endoplasmic reticulum (ER) stress, inhibited cell migration, reduced the % of ALDH positive cells in the population and enhanced PARP1 cleavage. 

Conclusion: The synergistic effect of the niraparib + F7 may result from the treatment affecting multiple genetic pathways involving cell death and reducing mesenchymal characteristics.”

https://pubmed.ncbi.nlm.nih.gov/38322025/

“Cannabis sativa is utilized worldwide for palliative care and to alleviate various symptoms associated with medical conditions. Several dozen compounds are biosynthesized in the female inflorescence of each C. sativa strain. In total, around 600 different molecules can be found in cannabis, among them around 150 phytocannabinoids and hundreds of flavonoids and terpenes

Multiple studies suggest that phytocannabinoids have anti-cancer properties.

They inhibit several different features associated with cancer cells and tumors, including inhibiting cell proliferation and migration, inducing cell death, reducing angiogenesis, and inhibiting cancer cells’ invasiveness. This was demonstrated in several different cancer types, including cancers of the skin, lung, breast, prostate, and brain.

The best-studied anti-cancer activity is that of the most common phytocannabinoids cannabidiol (CBD) and Δ9–tetrahydrocannabinol (THC), and related synthetic compounds (e.g., HU-210 and WIN-55 212-2).

Phytocannabinoids have been found to affect cancer cells and tumors via several different genetic pathways and molecular mechanisms. For example, several signal transduction pathways can be activated by phytocannabinoids to induce cancer cell death, including cell cycle arrest, endoplasmic reticulum (ER) stress, oxidative stress, autophagy and/or apoptosis.”

https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1333964/full


Antiviral Activities of Cannabis

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“Despite the history of scientific evidence regarding plants and their products in prophylactics and therapeutics, their applications in healthcare systems are only now gaining momentum.

Plants contain bioactive compounds that target certain viruses to cure or prevent viral diseases and infections.

They provide a rich resource of antiviral drugs. Identifying the antiviral mechanisms in plants has shed light on where they interact with the life cycle of viruses, such as viral entry, replication, assembly, and release.”

https://link.springer.com/chapter/10.1007/978-3-031-35155-6_13

Development and preliminary validation of the positive consequences of cannabis (PCOC) scale

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“Introduction: While extensive research exists on the negative consequences of cannabis use, there is a noticeable gap in the literature regarding positive consequences on patterns of cannabis use. The goal of the present study was to develop and test the psychometric properties of a novel scale, the Positive Consequences of Cannabis scale (PCOC) to assess positive outcomes of cannabis use among current adult cannabis users.

Methods: Participants (n = 768) were recruited through online platforms. The sample was predominantly non-Hispanic (92.3 %) male (62.92 %) with an average age of 29.08 years (SD = 6.10). A split half validation method was used to assess the factor structure of the PCOC scale. Data analysis also included Exploratory factor analysis (EFA) to identify underlying factor structures of the PCOC, confirmatory factor analysis (CFA) to validate the factor structure, and the assessments of internal consistency and validity.

Results: The EFA identified a two-factor solution for the PCOC: Social and Psychological Consequences and Cognitive and Motivational Consequences. The CFA confirmed the validity of this factor structure with good model fit (χ2 = 321.33, p < 0.001; CFI = 0.95; TLI = 0.95; RMSEA = 0.038; SRMR = 0.048). Internal consistency coefficients for the PCOC subscales and total scale exceeded acceptable thresholds. A hierarchical regression model showed that both PCOC subscales were significantly associated with cannabis use frequency and quantity.

Discussion: The development and validation of the PCOC represent a significant advancement in assessing positive consequences in understanding cannabis use patterns, indicating that individuals who experience a range of positive effects are more likely to engage in more frequent and intense cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/38295608/

https://www.sciencedirect.com/science/article/abs/pii/S0306460324000261?via%3Dihub

Unravelling the landscape of Cannabis craving pharmacological treatments: a PRISMA-guided review of evidence

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“Currently, few treatments are available for craving in general, and none of them have received approval for cannabis craving.

The objective of this review is to evaluate existing studies analysing treatments for cannabis craving and explore novel treatment possibilities for these patients.

The current pharmacological treatments largely involve off-label drug use and the utilisation of cannabinoid-based medications, such as combinations of THC and lofexidine, oxytocin, progesterone, and N-acetylcysteine.

These emerging treatments show promise and have the potential to revolutionise current clinical practices, but further investigation is needed to establish their efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38299652/

https://www.tandfonline.com/doi/full/10.1080/09540261.2023.2231540

Cannabis sativa: origin and history, glandular trichome development, and cannabinoid biosynthesis

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“Is Cannabis a boon or bane? Cannabis sativa has long been a versatile crop for fiber extraction (industrial hemp), traditional Chinese medicine (hemp seeds), and recreational drugs (marijuana). 

Cannabis faced global prohibition in the twentieth century because of the psychoactive properties of ∆9-tetrahydrocannabinol; however, recently, the perspective has changed with the recognition of additional therapeutic values, particularly the pharmacological potential of cannabidiol.

A comprehensive understanding of the underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources. Here, we comprehensively review the historical usage of Cannabis, biosynthesis of trichome-specific cannabinoids, regulatory network of trichome development, and synthetic biology of cannabinoids.

This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids, and the development and utilization of novel Cannabis varieties.”

“Historically, Cannabis use has encompassed various productive and religious purposes, playing a crucial role in diverse aspects of people’s lives.”

“Remarkable advancements in the cultivation of Cannabis plants with high-yielding cannabinoids and the reconstruction of cannabinoid production in microorganisms via metabolic engineering have been achieved.”

“In conclusion, Cannabis, an ancient medicinal plant with a longstanding history of global usage over millennia, can make a substantial transformative effect on human health in the future.”

https://academic.oup.com/hr/article/10/9/uhad150/7231120?login=false

“Cannabis sativa: Historical significance, genetic insights, and future potential in medicine and horticulture”

https://phys.org/news/2024-01-cannabis-sativa-historical-significance-genetic.html

Cannabis use among cancer patients and survivors in the United States: a systematic review

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“Background: How cannabis products are being used by cancer patients and survivors in the U.S is poorly understood. This study reviewed observational data to understand the modes, patterns, reasons, discontinuation and adverse experiences of cannabis use.

Methods: PubMed and PsycINFO database searches were conducted between May 2022 and November 2022. Of the 1,162 studies identified, 27 studies met the inclusion criteria. The inter-coder agreement was strong (0.81).

Results: The majority of the studies (74%) were cross-sectional in design. Study samples were approximately equal proportions of men and women and majority White participants. The prevalence of cannabis use based on national samples ranged between 4.8% and 22%. The most common modes of cannabis intake were topical application (80%), smoking (73%), vaping (12%), and ingestion of edible products (10%). Younger age, male gender, being a current or former smoker, and higher socio-economic status were associated with greater likelihood of cannabis use. The main motive for cannabis use was management of symptoms due to cancer or cancer treatment such as pain, nausea, lack of sleep, and anxiety. A majority of the participants across studies reported that cannabis helped reduce these symptoms. Lack of symptom improvement, side effects such as fatigue and paranoia, cost, and social stigma were identified as some of the reasons for discontinuing cannabis use.

Conclusions: It appears that cannabis may help cancer patients and survivors manage symptoms. However, more longitudinal studies are needed to determine whether positive experiences of cannabis use outweigh adverse experiences over time in this vulnerable population.”

https://pubmed.ncbi.nlm.nih.gov/38291891/

https://academic.oup.com/jncics/advance-article/doi/10.1093/jncics/pkae004/7593795?login=false

Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine)

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“Background: Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis.

Methods: This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use.

Results: 259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2-6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3-58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6-52.8%) of their current analgesics. Age (β = – 0.3, CI – 0.6-0.0), higher pain severity (β = 0.4, CI 0.1-0.6) and previous cannabis use (β = 14.7, CI 5.1-24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier.

Conclusions: Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.”

https://pubmed.ncbi.nlm.nih.gov/38291451/

https://josr-online.biomedcentral.com/articles/10.1186/s13018-024-04558-6

Risk of motor vehicle collision associated with cannabis and alcohol use among patients presenting for emergency care

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“Background: The objective of this study was to examine the relationship between cannabis and alcohol use and occurrence of motor vehicle collision (MVC) among patients in the emergency department (ED).

Methods: This was a cross-sectional study of visits to EDs in Denver, CO, Portland, OR, and Sacramento, CA by drivers who were involved in MVCs and presented with injuries (cases) and non-injured drivers (controls) who presented for medical care. We obtained blood samples and measured delta-9-THC and its metabolites. Alcohol levels were determined by breathalyzer or samples taken in the course of clinical care. Participants completed a research-assistant-administered interview consisting of questions about drug and alcohol use prior to their visit, context of use, and past-year drug and alcohol use. Multiple logistic regression was used to estimate the association between MVC and cannabis/alcohol use, adjusted for demographic characteristics. We then stratified participants based on levels of cannabis use and calculated the odds of MVC across these levels, first using self-report and then using blood levels for delta-9-THC in separate models. We conducted a case-crossover analysis, using 7-day look-back data to allow each participant to serve as their own control. Sensitivity analyses examined the influence of usual use patterns and driving in a closed (car, truck, van) versus open (motorcycle, motorbike, all-terrain vehicle) vehicle.

Results: Cannabis alone was not associated with higher odds of MVC, while acute alcohol use alone, and combined use of alcohol and cannabis were both independently associated with higher odds of MVC. Stratifying by level of self-reported or measured cannabis use, higher levels were not associated with higher odds for MVC, with or without co-use of alcohol; in fact, high self-reported acute cannabis use was associated with lower odds of MVC (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.05-0.65). In the case-crossover analysis, alcohol use alone or in combination with cannabis was associated with higher odds of MVC, while cannabis use alone was again associated with decreased odds of MVC.

Conclusions: Alcohol use alone or in conjunction with cannabis was consistently associated with higer odds for MVC. However, the relationship between measured levels of cannabis and MVC was not as clear. Emphasis on actual driving behaviors and clinical signs of intoxication to determine driving under the influence has the strongest rationale.”

https://pubmed.ncbi.nlm.nih.gov/38277855/

“Decades of research have established that alcohol increases the risk for motor vehicle collision (MVC) in a dose-dependent manner.”

“Cannabis alone was not associated with higher odds of MVC,”

https://www.sciencedirect.com/science/article/abs/pii/S0001457524000046?via%3Dihub