Category Archives: Chronic Pain

Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids

Posted on by
Reply
pubmed logo

“Pain impacts billions of people worldwide, but treatment options are limited and have a spectrum of adverse effects. The search for safe and nonaddictive pain treatments has led to a focus on key mediators of nociceptor excitability.

Voltage-gated sodium (Nav) channels in the peripheral nervous system-Nav1.7, Nav1.8, and Nav1.9-play crucial roles in pain signaling. Among these, Nav1.8 has shown promise due to its rapid recovery from inactivation and role in repetitive firing, with recent clinical studies providing proof-of-principal that block of Nav1.8 can reduce pain in humans.

We report here that three nonpsychotomimetic cannabinoids-cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN)-effectively inhibit Nav1.8, suggesting their potential as analgesic compounds.

In particular, CBG shows significant promise due to its ability to effectively inhibit excitability of peripheral sensory neurons. These findings highlight the therapeutic potential of cannabinoids, particularly CBG, as agents that may attenuate pain via block of Nav1.8, warranting further in vivo studies.”

https://pubmed.ncbi.nlm.nih.gov/39835903/

“Chronic pain is a major health problem worldwide; however, treatment options remain limited and often involve adverse side-effects or addiction risk. Targeting voltage-gated sodium (Nav) channels in sensory neurons, particularly Nav1.8, represents a promising therapeutic approach. Our work demonstrates that nonpsychotomimetic cannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), effectively inhibit Nav1.8. CBG, in particular, exhibits a potent inhibition of dorsal root ganglion neuron excitability, suggesting its potential as a nonaddictive analgesic. Our findings open different avenues for the development of cannabinoid-based treatments for pain therapy, with a focus on Nav1.8 inhibition as a therapeutic target.”

https://www.pnas.org/doi/10.1073/pnas.2416886122

[Impact of dronabinol shortage on a population of chronic pain patients: A retrospective observational study]

Posted on by
Reply
pubmed logo

“Objective: A supply shortage of dronabinol occurred between December 2023 and February 2024, forcing chronic pain patients to discontinue this treatment. We assessed the impact of this shortage on patients in our hospital.

Method: A retrospective observational study of patients treated with dronabinol was conducted. Collected data included socio-demographic, pharmacological and clinical data. Pain intensity and its interference, the intensity of other pain dimensions (mood, relationship with others, etc.) and quality of sleep were collected before discontinuation (dronabinol dosage balanced, M0) and at the end of discontinuation (dronabinol stopped for several weeks, M3). The patient’s perception of his state of health evolution was collected at the end of the shortage.

Results: Health deterioration was reported by 86% of patients after 3 months of rupture. Pain intensity and its interference with patients’ daily lives increased significantly. Patients’ sleep deteriorated significantly. The number of patients with permanent pain increased 5-fold (n=2 at M0 and n=10 at M3). The number of patients with more than 20 painful attacks per 24hours increased 2-fold (n=2 at M0 and n=4 at M3).

Conclusion: Although data on the efficiency of dronabinol are currently limited, this supply disruption has had negative clinical consequences for our patients. With drug shortages multiplying in recent years, the marketing of new specialties and therefore the availability of therapeutic alternatives could help reduce the clinical impact of a possible new dronabinol shortage in these refractory chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/39824703/

https://www.sciencedirect.com/science/article/abs/pii/S0040595724002191?via%3Dihub

“Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns”

https://pubmed.ncbi.nlm.nih.gov/26775260/

Emerging trends in cannabis administration for women with chronic pain

Posted on by
Reply
pubmed logo

“Cannabis use among women who experience chronic pain is on the rise in the United States. However, little is known about women’s motives and preferences for cannabis administration. The purpose of this study was to characterize cannabis use among women with chronic pain.

This study examined self-reported forms of cannabis administration and preferred source of cannabis, frequency and quantity of use, and self-reported side effects, and type, level, and intensity of chronic pain among adult women in the United States. This study also compared women who use cannabis for chronic pain and those who do not across the level of chronic pain, length of chronic pain, and the number of types of chronic pain experienced.

Participants showed a significant preference (60%) for using recreational cannabis to treat chronic pain but reported that medical cannabis was more effective. For participants who preferred medical cannabis 24.3% reported daily use, as compared to only 7.8% of recreational cannabis users. Smoking was the most common form of administration (62.1%), followed by edibles (25.3%), vaporizing in any form (7.4%), tinctures and concentrates (3.2%), and topicals (2.1%). Participants reported using 1-6 different forms of cannabis administration. Those who preferred smoking were significantly likely to use all other forms of administration. However, those who preferred alternatives to smoking were significantly likely to use all forms of administration except for smoking. Medical cannabis users preferred to obtain cannabis from a dispensary, while recreational users preferred to obtain cannabis from unlicensed sources.

Additionally, participants who used cannabis for chronic pain reported a 74% reduction in past 30-day opioid use.

Future research is needed to investigate the health effects associated with single and combined forms of cannabis administration for women with chronic pain. Results can inform educational and intervention programs, treatment development, content regulation of products, policy formation, women’s health research, and public health guidelines.”

https://pubmed.ncbi.nlm.nih.gov/39816373/

https://onlinelibrary.wiley.com/doi/10.1002/mhs2.88

Effects of a Cannabinoid-Based Phytocomplex (Pain ReliefTM) on Chronic Pain in Osteoarthritic Dogs

Posted on by
Reply
pubmed logo

“Twenty-one adult crossbreed dogs with chronic pain due to severe osteoarthrosis were enrolled in the study (placebo vs. treatment groups). The dogs in the experimental group received the dietary supplement (Pain ReliefTM, Giantec, Isernia, Italy) for 30 days to evaluate its effects on metabolism and pain relief. During the trial, the Helsinki Chronic Pain Index significantly decreased (p < 0.01) in the experimental group, indicating reduced pain and improved quality of life. Additionally, the treated group showed improvements in oxidative stress, demonstrated by a reduction in reactive oxygen metabolites, and an increase in biological antioxidant potential. Interleukins 6 levels decreased in the treated group, while interleukins 10 levels increased, thus suggesting an anti-inflammatory effect of the supplement. Importantly, no adverse effects were observed. Results suggest that Pain ReliefTM is effective in ameliorating osteoarthritis in dogs, improving their quality of life.”

https://pubmed.ncbi.nlm.nih.gov/39795044/

“Chronic pain is one of the most disabling conditions in dogs, as it affects various aspects of a dog’s life and should be managed regardless of the severity of symptoms. This research investigates the effects of a cannabidiol-based nutritional supplement in dogs affected by severe osteoarthritis. The treated group showed a reduction in pain due to an improvement of some cytokines expression and oxidative status. This suggests that Pain ReliefTM possesses an anti-inflammatory effect and reduces pain perception in dogs, thereby enhancing their quality of life.”

https://www.mdpi.com/2076-2615/15/1/101

Exploring Natural Analgesics for Chronic Pain Management: Cannabinoids and Other Phytoconstituents

Posted on by
Reply
pubmed logo

“Chronic pain lasting more than three months or persisting after normal healing is a significant global health issue. In a healthcare system, it is crucial to ensure proper chronic pain management. Traditional pharmacological and non-pharmacological pain management techniques may not fully meet the requirements of physicians regarding effectiveness and safety. Therefore, researchers are exploring natural analgesics.

Plant-based phytoconstituents show promise in relieving chronic pain associated with various diseases.

This study aims to review the latest advances in discovering natural bioactive compounds that can help alleviate chronic pain. It discusses the pathways of chronic pain and a multifactorial treatment strategy. It also organizes data on using plant- derived substances, such as cannabinoids, terpenoids, phenolics, and crude extracts. Additionally, it delves into the pharmacodynamics of cannabinoids, including their route of administration and elimination.

The review presents the results of 22 clinical trials on various cannabinoids for pain relief. It is important to note that opioids and other alkaloids from plants are not covered in this article due to their primary use in controlling acute rather than chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/39779559/

https://www.eurekaselect.com/article/145464

Synergistic Pain-Reducing Effects of Bixa orellana (Chronic® and Chronic In®) and Cannabidiol-Rich Cannabis sativa Extracts in Experimental Pain Models

Posted on by
Reply
pubmed logo

“Background: The present study aimed to evaluate the potential synergy between pharmaceutical formulations containing Bixa orellana L. (granulated-CHR OR and injectable nanodispersion-CHR IN) in conjunction with a cannabidiol (CBD)-rich extract of Cannabis sativa L. (CSE) on experimental pain models in Wistar rats. 

Methods: Chemical analysis was performed using gas chromatography (GC-MS). The pain tests employed were acetic acid-induced writhing (injection i.p. of 0.9% acetic acid), formalin (solution 1%), hot plate (55 ± 0.5 °C), and cold-water tail withdrawal tests. 

Results: Chemical analyses by chromatography confirmed that the oil from B. orellana is rich in δ-tocotrienol (72.0 ± 1.0%), while the oil from Cannabis sativa highlighted the presence of cannabidiol (CBD). The results from the experimental pain tests indicated that the combined administration of formulations containing Bixa orellana and C. sativa, such as the granulated CHR OR (400 mg/kg, orally) with CSE (40 mg/kg, orally) or the nanodispersion CHR IN (10 mg/kg, intramuscularly) with CSE (40 mg/kg, orally), demonstrated significant results (p < 0.001) in pain reduction. Although the formulations containing Bixa orellana extract showed statistical significance in the tests when used in isolation, their effects were inferior compared to the combined use with CSE or the isolated use of CSE. These findings suggest that combining formulations containing extracts of these plant species may represent a viable therapeutic option, considering the synergistic action in reducing pain under the experimental conditions employed. 

Conclusions: these results imply that combining the phytocomplexes present in B. orellana and C. sativa may be a promising approach for pain treatment.”

https://pubmed.ncbi.nlm.nih.gov/39770552/

https://www.mdpi.com/1424-8247/17/12/1710

Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study

Posted on by
Reply
pubmed logo

“Background: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP.

Methods: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analysed.

Results: Among 826 eligible patients ≥18 years old, 529 (64%) were included for data analysis at first follow-up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60 ± 15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<0.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intention-to-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis.

Conclusion: Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids.

Significance: The findings in this retrospective study conducted in a real-world clinical setting suggest a favourable safety profile of cannabinoids. Moreover, one-sixth (intention-to-treat) and one-third (per-protocol) of patients with chronic pain refractory to conventional analgesics, or experiencing intolerable adverse effects, benefited significantly from therapy with oral cannabinoid regimens. Combination of THC and CBD seems overall more effective than cannabinoid monotherapy. Conduction of randomized controlled trials investigating safety and efficacy of cannabinoid therapy to diagnosis specific patient subgroups with comparable clinical and pathophysiological chronic pain characteristics is warranted, hence contributing further to the process of clinical evidence clarification currently in progress.”

https://pubmed.ncbi.nlm.nih.gov/36394124/

“In conclusion, oral cannabinoid therapy in general appears to be safe and effective for relief of chronic pain in some patients, including a subset of patients with cancer-related pain (9%), not responding adequately to conventional treatment regimens or experiencing intolerable AEs. Moreover, beneficial effects on sleep and QoL were reported by the patients receiving oral cannabinoid therapy, although the assessment was not performed in a validated manner. Hence, our study confirms previously reported findings related to patients with chronic pain receiving oral cannabinoid therapy and in that way the study contributes further to the evidence pyramid at the level of observational studies. “

https://onlinelibrary.wiley.com/doi/10.1002/ejp.2054

Cannabidiol induces autophagy via CB1 receptor and reduces α-synuclein cytosolic levels

Posted on by
Reply
pubmed logo

“Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases.

In our study, we used a neuroblastoma cell line that overexpresses wild-type α-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic α-synuclein.

Our results demonstrated that cannabidiol enhances the accumulation of LC3-II- and GFP-LC3-positive vesicles, which indicates an increase in autophagic flux. In addition, cannabidiol-treated cells showed a reduction in cytosolic α-synuclein levels. These effects were inhibited when the cells were treated with a CB1 receptor-selective antagonist, which indicates that the biological effects of cannabidiol are mediated via its interaction with CB1 receptor. Additionally, we also observed that cannabinoid compounds induce autophagy and α-synuclein degradation after they interact with the CB1 receptor.

In summary, our data suggest that cannabidiol induces autophagy and reduces cytosolic α-synuclein levels. These biological effects are mediated preferentially through the interaction of cannabidiol with CB1 receptors, and therefore, cannabinoid compounds that act selectively on this receptor could represent a new approach for autophagy modulation and degradation of protein aggregates.”

https://pubmed.ncbi.nlm.nih.gov/39710053/

https://www.sciencedirect.com/science/article/pii/S0006899324006693?via%3Dihub

Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

Posted on by
Reply
pubmed logo

“Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain.

Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD.

The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44-0.86], p < 0.0001).

Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/39627343/

“Oral treatment with synthetic CBD was associated with a significant reduction in pain in most of the patients with NPS included in our study, and led to improvements in most of the NPS-associated symptoms analyzed. Hence, synthetic oral CBD appears to be a safe and effective treatment option for NPS-associated pain, and may be an alternative to conventional analgesics for managing chronic pain in this pathology.”

https://www.nature.com/articles/s41598-024-79239-9

The Use of Cannabinoids in the Treatment of Peripheral Neuropathy and Neuropathic Pain: A Systematic Review

Posted on by
Reply
pubmed logo

“Purpose: Peripheral neuropathies are commonly occurring conditions that are chronic and debilitating for patients. Established nonsurgical treatments have yielded mixed and patient-dependent results. Although cannabinoids have demonstrated efficacy as a treatment for central neuropathic pain, the therapeutic potential of cannabis-based medications for the management of peripheral neuropathic pain caused by nerve injury, trauma, and other noncompressive etiologies has yet to be definitively established. This study aims to determine whether cannabinoids are a potentially effective treatment for pain and symptoms associated with peripheral neuropathy.

Methods: A systematic search was conducted by two independent reviewers across PubMed, Cochrane, Ovid Medline, and CINAHL to identify studies in accordance with the predetermined inclusion/exclusion criteria. Information regarding study design, medication, dosage, effect on neuropathic pain, and other related outcomes was extracted. Meta-analysis of pain scores was performed for seven studies, and descriptive statistics were used to summarize other study findings as appropriate.

Results: Of the 927 studies identified, 14 randomized controlled trials were included. Thirteen of 14 studies (79%) observed a statistically significant decrease in neuropathic pain score following treatment with a cannabinoid. Meta-analysis yielded a mean difference of -0.67 [-0.89, -0.45]) on a 0-10 scale compared with placebo. Improvements in secondary outcomes such as sleep, sensory symptoms, and quality of life were observed.

Conclusions: Our analysis of the literature shows that cannabis-based medicines may be effective in treating the pain and symptoms of peripheral neuropathy. These findings suggest the applicability of cannabis-based medicines for peripheral neuropathy.”

https://pubmed.ncbi.nlm.nih.gov/39570218/

https://www.jhandsurg.org/article/S0363-5023(24)00474-X/abstract