Category Archives: Chronic Pain

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

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“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

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“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

UK medical cannabis registry: A clinical outcome analysis of medical cannabis therapy in chronic pain patients with and without co-morbid sleep impairment

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“Introduction: Chronic pain (CP) affects 35.0%-51.3% of the UK population, with 67%-88% reporting sleep disturbances. Cannabis-based medicinal products (CBMPs) have shown therapeutic potential in managing CP. Evidence suggests poor sleep worsens pain perception; therefore, this study aimed to assess patient-reported outcome measures (PROMs) following CBMP treatment in CP patients with and without co-morbid sleep impairment.

Methods: A prospective cohort study of CP patients from the UK Medical Cannabis Registry was conducted. Participants were separated by baseline single-item sleep quality scale (SQS) score into sleep impaired (SQS ≤3) and unimpaired (SQS ≥4) cohorts. The primary outcome assessed changes in PROMs from baseline to 1-, 3-, 6-, and 12-months. Participants completed the following: SQS, General Anxiety Disorder-7, EQ-5D-5L, Brief Pain Inventory (BPI), and Short-Form McGill Pain Questionnaire-2. Significance was defined as p < 0.050.

Results: 1139 participants met the inclusion criteria (sleep impaired: n = 517, 45.4%; sleep unimpaired: n = 622, 54.61%). The sleep impaired cohort showed improvements in all PROMs at each follow-up (p < 0.010). The sleep unimpaired cohort showed similar results (p < 0.050), except in SQS and ED-5Q-5L: self-care and anxiety/depression scores (p > 0.050). However, the sleep impaired cohort observed greater improvements in BPI pain severity (p < 0.050) and SQS (p < 0.001) than the sleep unimpaired cohort at all follow-ups. 2817 adverse events were self-reported between both cohorts (p = 0.197).

Discussion: These findings align with literature that shows associated improvements in pain outcomes following CBMP administration. Sleep impaired individuals were more likely to experience greater pain severity improvements. However, this was not confirmed on multivariate logistic regression analysis and instead may be confounded by baseline pain severity.

Conclusion: Whilst these results show promise for the effects of CBMPs on CP, they must be examined within the limitations of the study design. These findings provide further evidence to support the design of subsequent randomized controlled trials to verify causality between CBMPs and pain outcomes.”

https://pubmed.ncbi.nlm.nih.gov/39545361/

“The results of this observational cohort study suggest an association between CBMP treatment and improvement in pain-specific and HRQoL PROMs in CP patients with and without co-morbid sleep impairment. Notably, those with co-morbid sleep impairment were associated with greater improvements in BPI pain severity, SQS, and PGIC than those without. However, this finding was not confirmed on multivariate analysis. Reported sleep quality did improve across the cohort from baseline, and when present was also associated with improvements in pain severity, suggesting that the effects of CBMPs on sleep may provide additional benefits for individuals with chronic pain beyond affecting the transmission of nociceptive signals. At the onset of treatment, however, other variables may be better prognostic markers for response to CBMP treatment, such as severe pain or anxiety at baseline. With respect to clinical significance, 44.10% report an improvement in the sleep impaired cohort at 1-months, declining to 24.56% at 12-months. Despite being limited by its observational design, the present study can be used to inform future RCTs, in addition to current clinical practice.”

https://onlinelibrary.wiley.com/doi/10.1111/papr.13438

Efficiency of cannabis and cannabidiol in managing chronic pain syndromes: A comprehensive narrative review

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“Chronic pain affects up to 40% of adults, contributing to high medical expenses, the loss of productivity, reduced quality of life (QoL), and disability. Chronic pain requires detailed diagnostic assessment, treatment and rehabilitation, yet approx. 80% of patients report inadequate pain management.

As new treatment options are needed, we aimed to explore the effectiveness of medical cannabis-based products in managing chronic pain, with a particular focus on treatment patterns.

We searched the PubMed, Scopus and Web of Science databases using keywords related to cannabinoids and chronic pain syndromes. In total, 3,954 articles were identified, and 74 studies involving 12,562 patients were included. The effectiveness of cannabis-based products varied across studies.

Cannabinoids were most effective in treating chronic secondary headache and orofacial pain, chronic secondary musculoskeletal pain, chronic secondary visceral pain, and chronic neuropathic pain. Properly qualifying patients is the first crucial step in managing chronic pain, considering pain characteristics, comorbidities and other treatment options.

Treatment should start with low doses of cannabinoids, which are then increased to achieve the desired therapeutic effect while minimizing adverse effects.This narrative review revealed significant gaps in the evidence regarding precise treatment patterns, particularly for the long-term maintenance treatment needed by patients with chronic pain.

Medical cannabis can be considered an option for carefully selected patients with chronic pain syndromes when other treatment options fail to achieve an adequate response, and when the potential benefits outweigh the risks. However, there is still a need for well-designed clinical research to establish the long-term efficacy and safety of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39499191/

“Medical cannabis can be considered an option in carefully selected patients with chronic pain syndrome for the management of chronic pain when other treatment options fail to achieve an adequate response, and when potential benefits outweigh the risks. Patients with chronic secondary headache and orofacial pain, chronic secondary visceral pain, chronic secondary musculoskeletal pain, and chronic neuropathic pain can benefit more than other groups of patients experiencing chronic pain.”

https://dmp.umw.edu.pl/en/article/2024/61/5/765/

Cannabis-Based Phytocannabinoids: Overview, Mechanism of Action, Therapeutic Application, Production, and Affecting Environmental Factors

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“This review provides an overview of cannabis-based phytocannabinoids, focusing on their mechanisms of action, therapeutic applications, and production processes, along with the environmental factors that affect their quality and efficacy.

Phytocannabinoids such as THC (∆9-tetrahydrocannabinol), CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene) exhibit significant therapeutic potential in treating various physical and mental health conditions, including chronic pain, epilepsy, neurodegenerative diseases, skin disorders, and anxiety.

The cultivation of cannabis plays a crucial role in determining cannabinoid profiles, with indoor cultivation offering more control and consistency than outdoor methods. Environmental factors such as light, water, temperature, humidity, nutrient management, CO2, and the drying method used are key to optimizing cannabinoid content in inflorescences.

This review outlines the need for broader data transfer between the health industry and technological production, especially in terms of what concentration and cannabinoid ratios are effective in treatment. Such data transfer would provide cultivators with information on what environmental parameters should be manipulated to obtain the required final product.”

https://pubmed.ncbi.nlm.nih.gov/39457041/

“Phytocannabinoids, including THC, CBD, CBG, CBN, and CBC, present broad therapeutic potential in a wide range of physical and mental conditions. They have shown efficacy in treating chronic pain, reducing seizure activity, slowing neurodegenerative processes, psoriasis, acne, loss of appetite, sleep disorders, and psychosis. Dose dependence was notable in most cases, and thus, this requires careful management.”

https://www.mdpi.com/1422-0067/25/20/11258

Changes in Pain and Mental Health Symptoms Associated with Prescribed Medicinal Cannabis Use: A One-Year Longitudinal Study

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“Chronic pain and mental health issues like depression and anxiety significantly contribute to disease burden in Western countries.

While cannabinoids are suggested to have analgesic, anxiolytic and antidepressant properties, evidence, especially for long-term use, is inconclusive. This 12-month observational study evaluated the effects of prescribed medicinal cannabis for 96 patients suffering from pain, as well as sleep disturbances, depression and anxiety. Treatment outcomes for pain, depression, anxiety and sleep problems were assessed at 3, 6, and 12 months using validated instruments.

Significant reductions were observed in pain scores and the interference of pain on daily functions, alongside improvements in mental health and sleep. Many patients reported notable improvements in pain severity and reduced use of pain medications in the first 6 months, with a decline at 12 months. Additionally, sustained improvements in depression, anxiety, stress and sleep were observed, with about half reporting substantial improvement. Adverse effects were common but mostly mild or moderate, most commonly dry mouth and sleepiness.

These results show that prescribed medicinal cannabis treatment is associated with improvements in chronic pain and mental health symptoms, such as depression, anxiety and stress. However, findings also suggest reduced effectiveness with longer-term use, emphasizing the need for additional research.”

https://pubmed.ncbi.nlm.nih.gov/39432717/

“Cannabis is a plant that has been used for thousands of years as a traditional medicine to treat various medical ailments, including pain.

Overall, we found that the use of medicinal cannabis was associated with reduced pain during the first 6 months and improved mental well-being over 12 months. Patients reported not only less pain but also experienced reduced interference from pain in their daily functions. Furthermore, they reported decreased use of pain medications and a large proportion felt that their pain symptoms had significantly improved, as reflected in their reported changes in the severity of pain.”

https://www.tandfonline.com/doi/full/10.1080/15360288.2024.2414898

An early economic analysis of medical cannabis for the treatment of chronic pain

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“Background: Cannabis-based medicinal products (CBMPs) are increasingly demonstrating effectiveness in treating a wide range of conditions, with a relatively high safety profile in clinical usage compared to other prescription pain medications and few contraindications. Consultation and other prescription-related costs are, at present, higher for CBMPs than for some other treatment options, leading to some concern around wider prescribing.

Research design and methods: An early cost-effectiveness model was developed to estimate the impact of prescribing CBMPs alone and/or in addition to analgesics, physiotherapy, and cognitive behavioral therapy for chronic pain in the UK for 1 year.

Results: Due to their comparative effectiveness, CBMPs were found to be cost saving. Various scenarios were model tested; in all scenarios where CBMPs decrease pain-level states, less resource use is required. Increased efficacy of 5% was conservatively assumed based on current Real-World Evidence. In this scenario, CBMPs were significantly more cost-effective, and as costs relating to the prescribing of these continue to fall, relative savings are predicted to increase.

Conclusion: These findings highlight the substantial cost saving that CBMPs may represent for the treatment of chronic pain patients, and the benefits for healthcare providers as a treatment for this often hard-to-treat population.”

https://pubmed.ncbi.nlm.nih.gov/39415537/

https://www.tandfonline.com/doi/full/10.1080/14737167.2024.2412248

Prevalence and Effect of Cannabinoids in Pain Management for Hand Pathologies

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“Background: Cannabinoids are a diverse group of compounds under investigation for various medical purposes, including analgesia. Given the evolving landscape of cannabinoid use, we aimed to analyze their prevalence and effect in pain management among urban orthopedic hand patients.

Methods: An electronic survey was administered to 122 new patients presenting to the orthopedic hand clinic of a major urban academic hospital. Demographic data, numerical rating scale pain scores, cannabinoid usage, and other concomitant pain regimens were recorded.

Results: Approximately half of the new patients were dissatisfied with current pain management for their hand pathology. Prescription (Rx) and over-the-counter (OTC) pain medications were used by 58% (71/122) of patients, while cannabinoids were used by 15% (18/122) of patients. Compared with pre-usage pain scores, both cannabinoids and Rx/OTC medications induced significant reductions in pain associated with patients’ hand pathologies (Cannabinoid: Δ4.4, P = .002; Rx/OTC: Δ3.0, P < .001). Cannabinoids induced a larger analgesic effect, but this difference was not statistically or clinically significant (P = .06). Subjectively, cannabinoid users either preferred their cannabinoid over Rx/OTC medications or liked both equally. Opioid use was higher among cannabinoid users (22.2% vs 12.5%), although this was not statistically significant (P = .28).

Conclusion: Approximately 15% of new urban hand patients use cannabinoids for pain control, and these compounds have similar analgesic efficacy in hand pathologies as Rx/OTC medications. Cannabinoids are equally liked or preferred relative to traditional medications in this cohort, and they may play an important role in pain management for hand patients.”

https://pubmed.ncbi.nlm.nih.gov/39392237/

https://journals.sagepub.com/doi/10.1177/15589447241284275

Edible cannabis for chronic low back pain: associations with pain, mood, and intoxication

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“Introduction: Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown.

Methods: Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD).

Results: 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p < .05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p < .001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p < .05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p = .07).

Discussion: These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain.”

https://pubmed.ncbi.nlm.nih.gov/39380911/

“In this naturalistic observational study, it was found that the use of edible cannabinoid products significantly reduced chronic pain in extended and acute use models. More specifically, THC dose was associated with the greatest decrease in pain during the acute use session. Further, there was signal that more frequent use of a CBD-dominant product may provide stronger relief over a 2-week ad libitum use period.

These results indicate that edible cannabis may be a safe and suitable alternative pain therapy for those looking to substitute more traditional pain medications.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1464005/full

Identification of the TRPA1 Cannabinoid-Binding Site

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“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