Therapeutic potential of cannabis for surgical wound healing in rats

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“This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds.

An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis.

The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05).

To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.”

https://pubmed.ncbi.nlm.nih.gov/39296630/

http://vetmed.agriculturejournals.cz/artkey/vet-202408-0002_therapeutic-potential-of-cannabis-for-surgical-wound-healing-in-rats.php

Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome

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“Brain aging is associated with cognitive decline, reduced synaptic plasticity, and altered metabolism. The activity of mechanistic target of rapamycin (mTOR) has a major impact on aging by regulating cellular metabolism. Although reduced mTOR signaling has a general antiaging effect, it can negatively affect the aging brain by reducing synaptogenesis and thus cognitive functions. Increased mTOR activity facilitates aging and is responsible for the amnestic effect of the cannabinoid receptor 1 agonist Δ9-tetrahydrocannabinol (THC) in higher doses.

Long-term low-dose Δ9-THC had an antiaging effect on the brain by restoring cognitive abilities and synapse densities in old mice.

Whether changes in mTOR signaling and metabolome are associated with its positive effects on the aging brain is an open question. Here, we show that Δ9-THC treatment has a tissue-dependent and dual effect on mTOR signaling and the metabolome.

In the brain, Δ9-THC treatment induced a transient increase in mTOR activity and in the levels of amino acids and metabolites involved in energy production, followed by an increased synthesis of synaptic proteins. Unexpectedly, we found a similar reduction in the mTOR activity in adipose tissue and in the level of amino acids and carbohydrate metabolites in blood plasma as in animals on a low-calorie diet.

Thus, long-term Δ9-THC treatment first increases the level of energy and synaptic protein production in the brain, followed by a reduction in mTOR activity and metabolic processes in the periphery.

Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective antiaging and pro-cognitive medication.”

https://pubmed.ncbi.nlm.nih.gov/39296258/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00002

Measuring the Impact of Medical Cannabis Law Adoption on Employer-Sponsored Health Insurance Costs: A Difference-in-Difference Analysis, 2003-2022

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“Introduction: Recent studies suggest that medical cannabis laws may contribute to a relative reduction in health insurance costs within the individual health insurance markets at the state level. We investigated the effects of adopting a medical cannabis law on the cost of employer-sponsored health insurance in the United States.

Methods: We analyzed state-level data from the Medical Expenditure Panel Survey-Insurance Component (MEPS-IC) Private Sector spanning from 2003 to 2022. The outcomes included log-transformed average total premium costs per employee for single, employee-plus-one, and family coverage plans. We utilized the Sun and Abraham (J Econometr 225(2):175-199, 2021) difference-in-difference (DiD) method, looking at the overall DiD and event-study DiD. Models were adjusted for various state-level demographics and dichotomous policy variables, including whether a state later adopted recreational cannabis, as well as time and unit fixed effects and population weights.

Results: For states that adopted a medical cannabis law, there was a significant decrease in the log average total premium per employee for single (-0.034, standard error [SE] 0.009 (-$238)) and employee-plus-one (-0.025, SE 0.009 (-$348)) coverage plans per year considering the first 10 years of policy change compared with states without such laws. Looking at the last 5 years of policy change, we saw increases in effect size and statistical significance. In-time placebo testing suggested model robustness. Under a hypothetical scenario where all 50 states adopted medical cannabis in 2022, we estimated that employers and employees could collectively save billions on healthcare coverage, potentially reducing healthcare expenditure’s contribution to GDP by 0.65% in 2022.

Conclusion: Adoption of a medical cannabis law may contribute to decreases in healthcare costs. This phenomenon is likely a secondary effect and suggests positive externalities outside of medical cannabis patients.”

https://pubmed.ncbi.nlm.nih.gov/39287774/

Phytochemistry and pharmacological activities of Cannabis sativa fruit (Cannabis Fructus)

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“Cannabis sativa fruit (Cannabis Fructus) refers to the dried and ripe fruit of Cannabis sativa L. It is widely distributed in the northeast, North, and South China. It has medicinal, ecological, and economic values.

This study aimed to review the chemical constituents and pharmacological activities of Cannabis Fructus, providing a reference for further exploration of Cannabis Fructus. Comprehensive information on Cannabis Fructus was collected via electronic searches (e.g., Google Scholar, PubMed, Sci Finder, and Web of Science) and from books on phytochemistry.

Cannabis Fructus contains various compounds such as phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins, and polysaccharides. Its active ingredients exhibit anti-inflammatory, anti-oxidant, anti-bacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotective, lipoid-regulating, hepatoprotective, and immunomodulatory properties.”

https://pubmed.ncbi.nlm.nih.gov/39278423/

“Highlights

  • •Cannabis Fructus is the dried and ripe fruit of Cannabis sativa L, it has a long history of medicinal and edible use.
  • •Compounds in Cannabis Fructus include phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins and polysaccharides.
  • •Cannabis Fructus and its active ingredients have anti-inflammatory, antioxidant, antibacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotection, lipoid-regulating and liver-protecting activities and immunomodulatory activities.
  • •Cannabis Fructus can be used as the main raw material in the development of food, medicine, cosmetics, health products industry.”

https://www.sciencedirect.com/science/article/abs/pii/S0367326X24003976?via%3Dihub

Disease-Modifying Symptomatic Treatment (DMST) Potential of Cannabinoids in Patients with Multiple Sclerosis

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“With the recent introduction of a number of highly effective disease-modifying treatments (DMTs) and the resulting almost complete prevention of acute relapses in many patients with multiple sclerosis (MS), the interest of MS clinicians has gradually shifted from relapse prevention to counteraction of disease progression and the treatment of residual symptoms.

Targeting the cannabinoid system with nabiximols is an approved and effective strategy for the treatment of spasticity secondary to MS.

Recently, the concept of spasticity plus syndrome (SPS) was introduced to account for the evidence that spasticity often appears in MS patients in clusters with other symptoms (such as pain, bladder dysfunction, sleep, and mood disorders), where cannabinoids can also be effective due to their broader action on many immune and neuronal functions. Interestingly, outside these symptomatic benefits, extensive pre-clinical and clinical research indicated how the modulation of the cannabinoid system results in significant anti-inflammatory and neuroprotective effects, all potentially relevant for MS disease control.

This evidence makes nabiximols a potential disease modifying symptomatic treatment (DMST), a concept introduced in an attempt to overcome the often artificial distinction between DMTs and symptomatic therapies (STs).”

https://pubmed.ncbi.nlm.nih.gov/39279696/

https://www.eurekaselect.com/article/143047

Effectiveness of Cannabinoids Treatment in Pain Management and Other Fibromyalgia-Associated Symptoms: A Case Series

“Pharmacological therapies for FM are still ineffective in many patients, involving adverse effects that hinder their long-term use.

We aimed to assess the effectiveness of cannabinoids (Tilray Dried Flower THC18) in the management of chronic pain and other FM-associated symptoms according to patient-reported outcomes, in a series of three FM patients. 

We observed improvements after one and three months of cannabinoids treatment in Brief Pain Inventory (BPI), Visual Analogue Scale (VAS), Insomnia Severity Index (ISI), SF-36 Health Survey, and Fibromyalgia Impact Questionnaire (FIQ) allowing pain relief, and improvements in sleep quality, performance of daily life activities, and quality of life.

In conclusion, although more studies are needed, in our series of FM patients, cannabinoids treatment showed promising results in the management of chronic pain and other FM-associated symptoms, improving the quality of life of these patients.”

https://www.heraldopenaccess.us/openaccess/effectiveness-of-cannabinoids-treatment-in-pain-management-and-other-fibromyalgia-associated-symptoms-a-case-series

Cannabinoids in the Inflamed Synovium Can Be a Target for the Treatment of Rheumatic Diseases

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“The management of rheumatic diseases has noticeably changed in recent years with the development of targeted therapeutic agents, namely, biological disease-modifying antirheumatic drugs. Identifying essential signaling pathways and factors crucial for the development and progression of these diseases remains a significant challenge.

Therapy could be used to delay the onset or reduce harm. The endocannabinoid system’s presence within the synovium can be identified as a suggested target for therapeutic interventions due to its role in modulating pain, inflammation, and joint metabolism.

This review brings together the most pertinent information concerning the actions of the endocannabinoid system present in inflamed synovial tissue and its interaction with phytocannabinoids and synthetic cannabinoids, which can be used from a therapeutic perspective to minimize the inflammatory and pain processes typical of osteoarthritis and rheumatoid arthritis.”

https://pubmed.ncbi.nlm.nih.gov/39273304/

https://www.mdpi.com/1422-0067/25/17/9356

Changes in health-related quality of life over the first three months of medical marijuana use

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“Background: The psychosocial impact of medical marijuana use is not yet known. This study evaluated short-term changes in health-related quality of life (HRQoL) over the first three months of medical marijuana use.

Methods: This prospective, observational, longitudinal study followed adults newly recommended for medical marijuana by a physician for any of the more than 20 qualifying medical conditions in Pennsylvania. Participants (N = 438) provided their clinical status and demographic information, and completed semi-structured interviews prior to medical marijuana initiation (baseline) and at three months. HRQoL was assessed by the Short Form-36 (SF-36). Paired-samples t-tests evaluated changes in HRQoL over time.

Results: Participants (M age = 46.4 years [15.6]; 66.4% female) were mostly commonly referred for medical marijuana to treat anxiety disorders (61.9%) or severe chronic or intractable pain (53.6%). Participants reported rapid and significant improvements in all of the domains of HRQoL from baseline to three months after initiating medical marijuana use (physical functioning, role limitations due to physical health problems, emotional well-being, role limitations due to emotional problems, bodily pain, social functioning, energy/fatigue and general health, P < .001 for all). Age was negatively predictive of level of improvement over time for the physical functioning (P < .0001), role limitations due to physical health problems (P < .001), and pain (P < .0001) domains after controlling for baseline, with older participants displaying less improvement than younger participants.

Conclusions: Gains were observed in all HRQoL domains assessed after three months of medical marijuana use. In several domains, age was a significant predictor of degree of improvement.”

https://pubmed.ncbi.nlm.nih.gov/39256884/

“In conclusion, the use of medical marijuana for three months was associated with improvements in physical, social, emotional and pain-related HRQoL. Ongoing surveillance of HRQoL in individuals with physical and mental health conditions can help to treat the “whole person” and to capture any collateral impact of selected therapeutic approaches as treatment initiates and progresses. Results from this study can help patients, their caregivers, and their providers to make more informed and evidence-based decisions on whether to incorporate medical marijuana into their treatment regimens.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-024-00245-9

Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex

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“Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB1 receptors (CB1Rs). The action of CB1R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood.

In this study, we demonstrated that, at low doses, the CB1R agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST).

This effect is CB1R dependent because it was blocked by the CB1R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB1R-dependent mechanism.

Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB1R-independent mechanism. The CB1R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB1R-dependent antidepressant-like effect in the FST.

These results demonstrate that CB1R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.”

“These results establish that low doses of a CB1R agonist elicit potent antidepressant-like behavior and enhance 5-HT neurotransmission, mediated by CB1R activation in the mPFCv. Conversely, high doses nullify antidepressant-like behavior and markedly attenuate 5-HT neurotransmission, an effect that appears to be instigated by a non-CB1R mechanism.”

https://pubmed.ncbi.nlm.nih.gov/17959812/

Medicinal cannabis extracts are neuroprotective against Aβ1-42-mediated toxicity in vitro

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“Background: Phytocannabinoids inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein β amyloid (Aβ). We characterised the capacity of five proprietary medical cannabis extracts, heated and non-heated, with varying ratios of cannabidiol and Δ9-tetrahydrocannabinol and their parent carboxylated compounds to protect against lipid peroxidation and Aβ-evoked neurotoxicity in PC12 cells.

Methods: Neuroprotection against lipid peroxidation and Aβ1-42-induced cytotoxicity was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ1-42 aggregation and fluorescence microscopy.

Results: Tetrahydrocannabinol (THC)/tetrahydrocannabinolic acid (THCA)-predominant cannabis extracts demonstrated the most significant overall neuroprotection against Aβ1-42-induced loss of PC12 cell viability. These protective effects were still significant after heating of extracts, while none of the extracts provided significant neuroprotection to lipid peroxidation via tbhp exposure. Modest inhibition of Aβ1-42 aggregation was demonstrated only with the non-heated BC-401 cannabis extract, but overall, there was no clear correlation between effects on fibrils and conferral of neuroprotection.

Conclusions: These findings highlight the variable neuroprotective activity of cannabis extracts containing major phytocannabinoids THC/THCA and cannabidiol (CBD)/cannabidiolic acid (CBDA) on Aβ-evoked neurotoxicity and inhibition of amyloid β aggregation. This may inform the future use of medicinal cannabis formulations in the treatment of Alzheimer’s disease and dementia.”

https://pubmed.ncbi.nlm.nih.gov/39243211/

“With access to approved pathways increasing globally, medicinal cannabis formulations are increasingly being used to treat neuropsychiatric conditions. With laboratory and animal studies now showing benefits of cannabis and cannabinoids in treating neurodegenerative diseases, this study investigated whether whole cannabis extracts could protection neuronal cells against the toxicity of a signature Alzheimer’s disease protein, beta (β) amyloid.

We found that cannabis extracts afforded neuronal cells protection against amyloid β toxicity, mostly in extracts with the major phytocannabinoid, Δ9-THC, or its parent compound, Δ9-THC-COOH. These results suggest that medicinal cannabis may have potential in the further treatment of dementia.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.14078