Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Identification of the TRPA1 Cannabinoid-Binding Site

Posted on by
Reply
pubmed logo

“Chronic pain accounts for nearly two-thirds of conditions eligible for medical cannabis licenses, yet the mechanisms underlying cannabis-induced analgesia remain poorly understood.

The principal phytocannabinoids, the psychoactive Δ9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD), exhibit comparable efficacy in pain management. Notably, THC functions as an agonist of cannabinoid receptor 1 (CB1), whereas CBD shows minimal activity on CB1 and CB2 receptors.

Elucidating the molecular targets through which phytocannabinoids modulate the pain system is required for advancing our understanding of the pain pathway and optimizing medical cannabis therapies.

Transient receptor potential ankyrin 1 (TRPA1), a pivotal chemosensor in the pain pathway, has been identified as a phytocannabinoid target. Unlike most TRPA1 activators, phytocannabinoid activation is not mediated through the electrophilic binding site, suggesting an alternative mechanism. Here, we identified the human TRPA1 channel cannabinoid-binding site (CBS) and demonstrated that mutations at residue Y840 abolished responses to both THC and CBD at saturating concentrations, indicating a shared primary binding site. Molecular modeling revealed distinct interactions of THC and CBD with the Y840 residue within the CBS. Additionally, CBD binds to the adjacent general anesthetic binding site at oversaturating concentrations.

Our findings define the CBS of TRPA1 as overlapping with and adjacent to binding sites for other allosteric activators, suggesting that TRPA1 possesses a highly adaptable domain for binding non-electrophilic activators. This underscores its unique role as a chemosensor in the pain pathway. Furthermore, our results provide new insights into the molecular mechanisms of cannabinoid-induced analgesia and identify novel targets for pain management therapies.”

https://pubmed.ncbi.nlm.nih.gov/39368566/

https://www.sciencedirect.com/science/article/pii/S104366182400389X?via%3Dihub

Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential

Posted on by
Reply
pubmed logo

“Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.”

https://pubmed.ncbi.nlm.nih.gov/39356097/

https://www.eurekaselect.com/article/141807

Cannabis sativa L. Extract Alleviates Neuropathic Pain and Modulates CB1 and CB2 Receptor Expression in Rat

Posted on by
Reply
pubmed logo

“Introduction: Cannabis sativa L. (CSL) extract has pain-relieving potential due to its cannabinoid content, so the effects of two CSL extracts on alleviating neuropathic pain were investigated in vivo. Methods and groups: Male Wistar rats (n = 130) were divided into groups and received vincristine (0.1 mg/kg) and gabapentin (60 mg/kg) to induce and relieve neuropathic pain or CSL extracts (D and B). The mRNA and protein expression of the cannabinoid receptors type 1 and 2 (CB1R, CB2R) were evaluated in the cerebral cortex, hippocampus, and lymphocytes. Behavioural tests (Tail-Flick and von Frey) were performed on all animals.

Results: VK-induced neuropathic pain was accompanied by decreased CB1R protein level and CB2R mRNA expression in the cortex. Gabapentin relieved pain and increased CB1R protein levels in the hippocampus compared to the vincristine group. Hippocampus CB1R protein expression increased with the administration of extract D (10 mg/kg, 40 mg/kg) and extract B (7.5 mg/kg, 10 mg/kg) compared to VK group. In the cerebral cortex CSL decreased CB1R protein expression (10 mg/kg, 20 mg/kg, 40 mg/kg of extract B) and mRNA level (5 mg/kg, 7.5 mg/kg of extract B; 20 mg/kg of extract D) compared to the VK-group.CB2R protein expression increased in the hippocampus after treatment with extract B (7.5 mg/kg) compared to the VK-group. In the cerebral cortex extract B (10 mg/kg, 20 mg/kg) increased CB2R protein expression compared to VK-group.

Conclusion: Alterations in cannabinoid receptor expression do not fully account for the observed behavioural changes in rats. Therefore, additional signalling pathways may contribute to the initiation and transmission of neuropathic pain. The Cannabis extracts tested demonstrated antinociceptive effects comparable to gabapentin, highlighting the antinociceptive properties of Cannabis extracts for human use.”

https://pubmed.ncbi.nlm.nih.gov/39334832/

“Furthermore, both tested Cannabis sativa L. extracts demonstrated antinociceptive effects comparable to gabapentin, highlighting the potential medical value of Cannabis extracts for human use.”

https://www.mdpi.com/2218-273X/14/9/1065

Exploring the therapeutic potential of cannabinoids in cancer by modulating signaling pathways and addressing clinical challenges

Posted on by
Reply
pubmed logo

“For centuries, cannabinoids have been utilized for their medicinal properties, particularly in Asian and South-Asian countries. Cannabis plants, known for their psychoactive and non-psychoactive potential, were historically used for spiritual and remedial healing. However, as cannabis became predominantly a recreational drug, it faced prohibition.

Recently, the therapeutic potential of cannabinoids has sparked renewed research interest, extending their use to various medical conditions, including cancer. This review aims to highlight current data on the involvement of cannabinoids in cancer signaling pathways, emphasizing their potential in cancer therapy and the need for further investigation into the underlying mechanisms.

A comprehensive literature review was conducted using databases such as PubMed/MedLine, Google Scholar, Web of Science, Scopus, and Embase. The search focused on peer-reviewed articles, review articles, and clinical trials discussing the anticancer properties of cannabinoids. Inclusion criteria included studies in English on the mechanisms of action and clinical efficacy of cannabinoids in cancer.

Cannabinoids, including Δ9-THC, CBD, and CBG, exhibit significant anticancer activities such as apoptosis induction, autophagy stimulation, cell cycle arrest, anti-proliferation, anti-angiogenesis, and metastasis inhibition. Clinical trials have demonstrated cannabinoids’ efficacy in tumor regression and health improvement in palliative care. However, challenges such as variability in cannabinoid composition, psychoactive effects, regulatory barriers, and lack of standardized dosing remain.

Cannabinoids show promising potential as anticancer agents through various mechanisms. Further large-scale, randomized controlled trials are essential to validate these findings and establish standardized therapeutic protocols. Future research should focus on elucidating detailed mechanisms, optimizing dosing, and exploring cannabinoids as primary chemotherapeutic agents.”

https://pubmed.ncbi.nlm.nih.gov/39331301/

https://link.springer.com/article/10.1007/s12672-024-01356-8

“Cannabis Compounds Show ‘Promising Potential As Anticancer Agents’”

https://www.forbes.com/sites/ajherrington/2024/10/08/cannabis-compounds-show-promising-potential-as-anti-cancer-agents/

Cannabinoids as a Natural Alternative for the Management of Neuropathic Pain: A Systematic Review of Randomized Placebo-Controlled Trials

Posted on by
Reply

“Dysfunction or damage to the nervous system may develop into and result in a chronic pain condition known as neuropathic pain. Neuropathic pain is defined as the structural and functional alteration of the somatosensory component of the nervous system. The treatment of neuropathic pain is a complex endeavor, which often requires specialist care and intensive drug therapy. Recently, cannabinoids have emerged as an alternative and natural option for the treatment of chronic pain, with tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most extensively studied neuroactive components. The therapeutic potential of cannabis remains largely underexplored, primarily due to its social stigma and the restrictions that are in place on its cultivation. The primary aim of this systematic review was to explore the therapeutic value of cannabinoids in the management of chronic pain and thus achieve an improved quality of life for those patients.

A systematic review of the literature published over the last two decades was performed using the following databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Turning research into practice (Trip), and Google Scholar. Studies that were completed and published between January 01, 2000 and August 31, 2024, in English language, were extracted and appraised. A combination of keywords and Boolean operators Cannabis OR Chronic Pain OR End of life OR Pain Management AND Drug therapy was employed for data extraction. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used for risk-of-bias assessment. The initial search resulted in 125282 articles; 86,781 of the articles were identified as duplicates and were removed from the primary analysis, and 38,501 abstracts were thus screened. Abstracts, case studies, reports, editorials, viewpoints, cross-sectional studies, cohort studies, case-control studies, case series, and letters to the editor/correspondence manuscripts (n =38,492) were furthermore excluded. Nine full-text articles were critically assessed and tested against the inclusion and exclusion criteria, and a further four articles were excluded with a total of five placebo-controlled randomized control studies being ultimately included in the final systematic review.

Compared to placebo, cannabinoids provided significant relief from chronic pain (33% vs 15%) as measured by the visual analog scale. The transdermal application of CBD led to a more pronounced reduction in sharp pain, according to the neuropathic pain scale. Minimal to no side effects were recorded, further highlighting the potential benefits of cannabinoids. 

The potential benefit of cannabinoids is that they are naturally derived drugs that have already been shown to have the potential to effectively decrease chronic pain with minimal side effects as compared to the standard drugs being used. The ability of cannabinoids to provide pain relief with minimal side effects and concurrently be a naturally derived product may potentially be a life-changing alternative that the pharmaceutical market is in dire need of.”

https://www.cureus.com/articles/297124-cannabinoids-as-a-natural-alternative-for-the-management-of-neuropathic-pain-a-systematic-review-of-randomized-placebo-controlled-trials#!/

Therapeutic potential of cannabis for surgical wound healing in rats

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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)

Posted on by
Reply
pubmed logo

“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

Posted on by
Reply
pubmed logo

“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