Category Archives: Chronic Pain

Medicinal use of non-prescribed cannabis: a cross-sectional survey on patterns of use, motives for use, and treatment access in the Netherlands

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“Background: Despite the Netherlands having one of the world’s oldest medical cannabis programs, the majority of people who use cannabis for medicinal purposes continue to rely on non-prescribed sources. This study investigates patterns of use, motives for use, perceived effectiveness, and barriers to accessing prescribed cannabis among individuals self-medicating with non-prescribed cannabis.

Methods: A cross-sectional online survey was conducted between January and April 2023, using convenience sampling primarily via social media. Participants (N = 1059) were adults (18 years or older) residing in the Netherlands who self-reported current use of non-prescribed cannabis-based products to manage physical or mental health symptoms.

Results: Cannabis was used to manage a wide range of conditions, most commonly chronic pain, sleep disorders, depression, and ADHD/ADD, with three out of four participants reporting use for multiple conditions. Most participants obtained cannabis from coffeeshops, although one in four also reported home cultivation as a source. Participants typically smoked cannabis with tobacco, reported (near-)daily use for therapeutic purposes, and indicated a monthly expenditure of €100. The majority was not aware of the THC and CBD content of their products. Perceived effectiveness was rated as high, and more than half of those with a history of prescription medication use reported substituting cannabis for these medications. Only a minority of participants had ever used, or were currently using, prescribed cannabis. Commonly cited barriers included perceived lower quality, higher cost, and lower ease of access compared with non-prescribed cannabis.

Conclusions: The widespread use of non-prescribed cannabis for medicinal purposes in the Netherlands reflects both unmet health needs and barriers within the regulated medical cannabis system. Risky use practices – such as smoking cannabis with tobacco and using products without knowing their cannabinoid content – raise public health concerns. The findings highlight the need for harm reduction strategies and policies that better align medical cannabis regulation with patients’ real-world behaviours and care needs.”

https://pubmed.ncbi.nlm.nih.gov/41331499

https://link.springer.com/article/10.1186/s42238-025-00355-y

Modulatory Effects of “Minor” Cannabinoids in an in vitro Model of Neuronal Hypersensitivity

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“Aim: Effective treatment for neuropathic pain remains an unmet clinical need. The therapeutic benefits of the Cannabis plant are well known, especially for pain relief. Here, we have assessed ten “minor” cannabinoids for their analgesic effects in an established model of neuronal hypersensitivity, a key mechanism which underlies neuropathic pain.

Methods: Adult rat DRG neurons were cultured in medium containing 100 ng/mL nerve growth factor (NGF) and 50 ng/mL glial cell-line derived neurotrophic factor (GDNF) for 48 hours to sensitize the neurons. Ca2+ imaging was used to measure the responses to pain stimulation using capsaicin, and to determine the modulatory effects of the cannabinoids, in individual neurons.

Results: Control neurons (nociceptors) showed robust responses of Ca2+ influx to capsaicin application, while neurons treated with ten minor cannabinoids tetrahydrocannabiorcol (THCC), cannabitriol (CBT), cannabidivarin (CBDV), cannabinol (CBN), cannabichromene (CBC), cannabichromevarin (CBCV), cannabicitran (CBCT), cannabigerol monomethyl ether (CBGM), tetrahydrocannabutol (THCB) or tetrahydrocannabiphorol (THCP), at concentrations of 0.001-100 μM, showed differential dose-related effects on the responses to capsaicin. Ca2+ influx in response to capsaicin application was completely inhibited for each compound in 35-78% capsaicin-sensitive neurons, while other neurons showed reduced responses. The opioid receptor agonist morphine and α2δ1- Ca2+ channel inhibitor gabapentin were also tested for comparison and showed similar results. All the cannabinoids tested here inhibited calcium influx in response to capsaicin, and two, namely, CBN and THCC elicited calcium influx at higher doses. Inhibition of Ca2+ influx due to cannabichromene (CBC) was reversed by the potassium channel inhibitor Tertiapin Q.

Conclusion: All the cannabinoids tested here inhibited TRPV1 signalling. CBC targeted K+ channels to block TRPV1 mediated Ca2+ influx, demonstrating potential analgesic effects in vitro.”

https://pubmed.ncbi.nlm.nih.gov/41322279

“The therapeutic benefits of the Cannabis plant are well known, especially for pain relief.”

“In conclusion, our results show that the minor cannabinoids potently inhibit TRPV1 signaling in sensitized DRG neurons, and for CBC by blocking Ca2+ influx via K+ channel activation. This conclusion is based on the reversal of CBC-mediated inhibition in the presence of the K+ channel inhibitor Tertiapin Q. Further studies are necessary to confirm the mechanism, pathways and targets involved in the observed inhibitory effects of the other minor cannabinoids. This will facilitate the identification of cannabinoid combinations likely to have the maximum effect in providing analgesia for inhibiting neuronal sensitization that underlies chronic pain.”

https://www.dovepress.com/modulatory-effects-of-minor-cannabinoids-in-an-in-vitro-model-of-neuro-peer-reviewed-fulltext-article-JPR

Use of Cannabidiol and Cannabigerol in the Treatment of Trigeminal Neuralgia and Postherpetic Pain

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“The use of cannabidiol (CBD) as an adjuvant in the treatment of trigeminal neuralgia (TN) and postherpetic neuropathy has shown beneficial effects in patients refractory to conventional treatments.

This case study describes a 57-year-old patient diagnosed with TN in 2019, initially treated with low-power laser therapy and oxcarbazepine. In 2021, she developed vesicular-bullous lesions on the right side of the supraorbital region, accompanied by severe pain confirmed by positive serology for shingles. Following the diagnosis of postherpetic neuropathy, the drug dose was adjusted and combined with laser therapy. However, the pain remained significant and reduced quality of life.

In 2023, treatment was started with CannaMeds CBD Full Spectrum – 3000 mg/30 ml + CannaMeds CBG Isolate 1500 mg/30 ml. After 15 days, the patient appeared pain-free, allowing the laser to be discontinued and the drug dose to be reduced.

CBD is a treatment option for patients who do not respond to conventional treatments.”

https://pubmed.ncbi.nlm.nih.gov/41281696

“It is difficult to find an effective treatment for these conditions, because over time patients no longer respond to treatment. Therefore, the use of CBD and cannabigerol could be an adjuvant treatment option for patients who do not respond to conventional treatment for neuropathic pain.”

https://journals.lww.com/cocd/fulltext/2025/07000/use_of_cannabidiol_and_cannabigerol_in_the.10.aspx

A Longitudinal Assessment of Endometriosis Patients Prescribed Cannabis-Based Medicinal Products: A Case Series From the UK Medical Cannabis Registry

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“Background: Although there is growing evidence supporting the use of cannabis-based medicinal products (CBMPs) for the management of chronic pain, there is a paucity of data on their effect on endometriosis-associated chronic pain.

Aims: This study aimed to perform an analysis of pain-specific and general health-related quality of life (HRQoL) outcomes for patients with endometriosis-associated chronic pain treated with CBMPs.

Materials and methods: Primary outcomes included changes in patient-reported outcome measures (PrOMs) from baseline to 1, 3, 6, 12 and 18 months. A repeated measures ANOVA was applied to assess changes in PrOMs at 1 to 18 months from baseline. Secondary outcomes included incidence and frequency of adverse events (AEs).

Results: Sixty-three patients met inclusion criteria. Initiation of CBMPs was associated with improvements in all pain-specific PrOMs from baseline to 18 months (p < 0.050). EQ-5D-5L index value showed improvements between baseline and all months (p < 0.050). Anxiety and sleep quality PrOMs showed improvements from baseline to 18 months (p < 0.050). Minimal clinically significant differences (11%-37%), moderately important improvements (5%-22%) and substantial improvements (0%-11%) were observed in the Brief Pain Inventory (BPI) and pain severity visual analogue scale. Sixty-two adverse events were reported by 16 (25.40%) participants.

Conclusions: This study observed an association between CBMP treatment and improvements in pain and HRQoL in patients with endometriosis. Causality cannot be inferred due to the nature of this observational study; however, these findings provide complementary evidence for the development of randomised controlled trials to assess the efficacy of CBMPs for endometriosis-associated chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/41305963

“Cannabis-based medicinal products (CBMPs) that contain phytocannabinoids, such as (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), have been identified with potential to manage endometriosis-related pain.”

“Overall, these results provide a signal towards improvement in short-term pain severity and interference for endometriosis patients after the initiation of CMBP treatment, although there was diversity at different pain intervals.”

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.70078

Minor Cannabinoids CBD, CBG, CBN and CBC differentially modulate sensory neuron activation

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“The use of minor cannabinoids has been advanced, in part, by the idea of providing relief from pain and inflammation without the burden of unwanted psychogenic effects associated with Δ 9 THC. In this regard, investigators have focused on the effects of minor cannabinoid activation / desensitization of peripheral sensory neurons on nociceptive signaling and/or peripheral inflammation.

With a focus on peripheral nociception, four common minor cannabinoids: cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN) and cannabichromene (CBC) were studied in primary cultures of mouse Dorsal Root Ganglion (DRG) neurons.

We queried if calcium responses induced by the four cannabinoids differed in potency of activation, neuronal size preference, and dose-response relationships. Additionally, we determined the dependence of CBD and CBN on key channel-receptors that are known to mediate pain and/or antinociception.

Individually, CBD, CBG and CBC directed greater response magnitudes when compared to CBN. All four minor cannabinoids activated overlapping but distinct size populations of sensory neurons. CBD and CBG activated the widest range of DRG neuron sizes (smaller-larger) overlapping with smaller capsaicin-sensitive neurons. In contrast, CBN and CBC activated predominantly larger sensory neurons. CBD diverged from other minor cannabinoids in directing a linear dose-response profile whereas CBG and CBC directed sigmoidal dose-response profiles and CBN activated DRG neurons with an inverted U-shaped dose-response relationship. CBD-induced activation of DRG neurons was dependent on co-expression of the nociceptive channel TRPV1 plus cannabinoid receptor 1 (CB 1 R), whereas CBN-induced activation was independent of TRPV1.

Overall, we observed that minor cannabinoids CBD, CBG, CBN and CBC differed in their activation of DRG neurons and directed unique activation properties across a diverse population of sensory neurons. Such differences underly the hypothesis that a combination (entourage) of complimentary minor cannabinoids can direct synergistic antinociceptive activity.”

https://pubmed.ncbi.nlm.nih.gov/41256665

https://www.biorxiv.org/content/10.1101/2025.10.02.680148v1

Sex differences in the capacity of minor phytocannabinoids to attenuate nociceptive insults in HIV-1 Tat-expressing mice

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“Objecives: Approximately 80 % of people living with HIV (PLWH) develop chronic pain and preclinical studies support the involvement of the HIV-1 regulatory protein, trans-activator of transcription (Tat). Phytocannabinoids may attenuate pain in PLWH; however, these data are controversial, and the biological mechanisms are difficult to untangle from psychosocial factors in people.

Methods: We have examined the therapeutic capacity of minor phytocannabinoids to attenuate Tat-promoted visceral hyperalgesia (acetic acid writhing assay) and reflexive nociception (warm water tail flick assay) in transgenic mice. We hypothesized that conditional expression of Tat1-86 in male and female mice [Tat(+) mice] would amplify pain responses compared to controls [Tat(-) mice], and that phytocannabinoids could ameliorate these effects.

Results: Irrespective of sex, Tat(+) mice demonstrated greater visceral pain responses than did Tat(-) controls. The phytocannabinoids, cannabigerolic acid (CBGA), cannabidiol (CBD), and cannabinol (CBN), attenuated Tat-induced visceral pain in both males and females. However, the effectiveness of these cannabinoids varied by sex with CBN being more efficacious in males, while cannabigerol (CBG) alleviated visceral pain only in Tat(+) females. Cannabidiolic acid (CBDA) and cannabidivarin (CBDV) were not effective in either sex. CBGA and CBG were also efficacious in the tail flick test among Tat(-) males and females, but demonstrated only small, sex-dependent effects to reverse Tat-induced nociception. CBD and CBN exerted little-to-no efficacy in this test.

Conclusions: These data suggest that phytocannabinoids exert analgesia for HIV-related pain, potentially aiding in the development of personalized pain management strategies.”

https://pubmed.ncbi.nlm.nih.gov/41221301/

“Overall, PLWH are more vulnerable to the development of chronic pain, resulting in physical disability and a reduced quality of life. The current pharmacological treatments for managing HIV-related pain lack efficacy and are associated with the risk of substance abuse. The medicinal use of non-psychoactive cannabis constituents for pain management might greatly benefit this population which is at a greater risk for opioid addiction and substance abuse.”

https://www.degruyterbrill.com/document/doi/10.1515/nipt-2024-0025/html

Dual Role of the Spinal Endocannabinoid System in Response to Noxious Stimuli: Antinociceptive Pathways and Neuropathic Pain Mechanisms

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“Neuropathic pain is a clinically challenging syndrome that is largely refractory to conventional therapies. It arises from lesions or diseases affecting somatosensory pathways, which trigger extensive neuroplastic and neuroimmune remodeling. Unlike nociceptive pain, which establishes a protective response to tissue injury, neuropathic pain arises from maladaptive signaling within the nervous system.

In this context, the spinal endocannabinoid system (ECS) has emerged as a pivotal modulator of nociceptive processing. However, its precise role in neuropathic pain remains debated due to its dual effects.

Numerous studies report antinociceptive and neuroprotective effects; however, emerging data indicate that under specific pathological conditions, ECS activation may paradoxically facilitate pain transmission.

This review examines spinal ECS context dependence, uncovering its bidirectional antinociceptive and pronociceptive effects in neuropathic pain. By integrating current evidence on cellular, molecular, and pathophysiological mechanisms, we delineate the factors that determine whether ECS modulation inhibits or promotes pain. A comprehensive understanding of these mechanisms is essential for optimizing cannabinoid-based strategies to maximize therapeutic benefits while minimizing adverse outcomes.

Finally, we highlight the spinal cord’s centrality as the principal site for the initiation and maintenance of neuropathic pain and advocate for rigorous translational research to clarify the therapeutic potential of spinal ECS-targeted interventions.”

https://pubmed.ncbi.nlm.nih.gov/41226728/

“From a therapeutic perspective, ECS duality represents both a challenge and an opportunity. Pharmacological manipulation of the ECS, through selective CB1R and CB2R agonists, FAAH and MAGL enzyme inhibitors, allosteric modulators, or combined strategies including glial modulators, constitutes a promising avenue for developing innovative treatments targeting neuropathic pain. However, the success of these interventions critically depends on a precise understanding of the pathophysiological context of eCB pathways and the evolutionary stage of the pathology.”

https://www.mdpi.com/1422-0067/26/21/10692

Therapeutic Potential of Cannabidiol-Rich Cannabis sativa to Mitigate the Severity of Inflammation and Pain: A Pre-Clinical Study

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“Ethnopharmacological relevance: Pain and inflammation are among the many conditions for which Cannabis sativa L. has historically been used. However, little research has been done on the potential therapeutic benefits of employing green extraction techniques to generate an extract from C. sativa that is high in cannabidiol for the treatment of severe pain and inflammation.

Aim of the study: This study investigates the potential chemico-pharmacological profile of a supercritical CO2 extract of Cannabis sativa genotype CIM-CS-64 (CSFE) for managing inflammation and pain responses using an experimental pharmacology approach.

Materials and methods: A combination of complementary analytical techniques (GC-FID, GC-MS, HPLC, HRMS, NMR) was used to examine the chemical composition of the CSFE to ensure comprehensive chemical coverage. The experiments were conducted on small laboratory animals to investigate the therapeutic efficacy of CSFE in mitigating inflammation and pain responses.

Results: Altogether, sixty-two compounds with cannabidiol, β-caryophyllene, cannabidivarin, cannabichromene, (E)-phytol, and α-bisabolol as major constituents were annotated in CSFE by GC-FID and GC-MS techniques. The HPLC analysis revealed the presence of CBD (9.75 ± 0.85%), CBDA (2.76 ± 0.69%) and Δ9-THC (4.40±0.16%) as major cannabinoids in the CSFE. In LPS-stimulated macrophages, the CSFE markedly reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) at concentrations of 3, 10, and 30 μg/ml without causing any cytotoxicity. The results demonstrated a significant decrease in inflammation and considerable improvement in pain-relieving potential in a dose-dependent manner.

Conclusions: The present research revealed that CSFE possesses promising analgesic and anti-inflammatory properties in small laboratory animals.”

https://pubmed.ncbi.nlm.nih.gov/41213439/

“Altogether, sixty-two compounds with cannabidiol, β-caryophyllene, cannabidivarin, cannabichromene, (E)-phytol, and α-bisabolol as major constituents were annotated in CSFE by GC-FID and GC-MS techniques.

The HPLC analysis revealed the presence of CBD (9.75 ± 0.85 %), CBDA (2.76 ± 0.69 %) and Δ9-THC (4.40 ± 0.16 %) as major cannabinoids in the CSFE. In LPS-stimulated macrophages, the CSFE markedly reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) at concentrations of 3, 10, and 30 μg/ml without causing any cytotoxicity.

The results demonstrated a significant decrease in inflammation and considerable improvement in pain-relieving potential in a dose-dependent manner.”

“The present research revealed that CSFE possesses promising analgesic and anti-inflammatory properties in small laboratory animals.”

“The findings validate the use of the plant for managing pain and inflammation in traditional medicine.”

https://www.sciencedirect.com/science/article/abs/pii/S037887412501548X?via%3Dihub

The impact of tetrahydrocannabinol on central pain modulation in chronic pain: a randomized clinical comparative study of offset analgesia and conditioned pain modulation in fibromyalgia

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“Tetrahydrocannabinol (THC) has shown efficacy in alleviating chronic pain, particularly in disorders characterized by central sensitization. Offset analgesia (OA) and conditioned pain modulation (CPM) are key biomarkers used to evaluate central pain modulation.

This study aimed to compare the effects of THC on OA and CPM in fibromyalgia syndrome (FMS), a prototypical condition of central sensitization.

Methods

In a randomized, double-blind, placebo-controlled crossover design, 23 FMS patients participated in two experimental sessions. Each session included the McGill Pain Questionnaire, visual analogue scale (VAS) assessments, and evaluations of OA and CPM, conducted both before and after sublingual administration of either THC (0.2 mg/kg) or placebo.

Results

THC significantly reduced spontaneous pain ratings on the McGill scale compared to both baseline and placebo (P = 0.01 and P = 0.02, respectively). THC also significantly enhanced OA relative to baseline and placebo (P = 0.04 and P = 0.008), while no effect was observed on CPM (P = 0.27). Notably, baseline OA magnitude significantly predicted THC-induced pain relief (R² = 0.404, P = 0.003), whereas CPM did not show a significant association (P = 0.121).

Conclusions

This is the first study to evaluate THC’s distinct effects on central pain modulation using both OA and CPM. THC selectively enhanced OA without influencing CPM, highlighting differential neural mechanisms underlying these paradigms. Furthermore, OA predicted treatment response, suggesting its potential as a biomarker for personalized cannabinoid-based therapies in FMS and other central sensitization disorders.”

https://pubmed.ncbi.nlm.nih.gov/41199355/

“Cannabis, particularly its psychoactive component delta-9-tetrahydrocannabinol (THC), has attracted increasing attention as a therapeutic option for chronic pain management. Clinically, THC has been shown to reduce pain intensity, improve quality of life and attenuate hyperalgesia in various chronic pain conditions, including neuropathic pain and fibromyalgia “

“THC is thought to exert its analgesic effects in part by modulating disrupted pain networks. Specifically, THC interacts with the endocannabinoid system.”

“To conclude, this study corroborates the possible effectiveness of THC in alleviating experimental and spontaneous pain in FMS, a study case of central sensitization, and shows an enhancement of OA responses after THC treatment in FMS patients compared to baseline and placebo.”

“This, in turn, reinforces the potential of OA as a reliable marker of pain modulation in FMS and may pave the way for personalized cannabinoid-based therapies for chronic pain in the future.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00348-x

Cannabis Use Patterns Among Adults Living With Chronic Pain Before and During the COVID Pandemic: Insights From the COVID-19 Cannabis Health Study

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“Background: This study aims to identify sociodemographic factors associated with cannabis use for chronic pain management before and after COVID-19 was declared a pandemic. Furthermore, it seeks to compare cannabis use patterns in adults with and without chronic pain.

Methods: We analyzed US-based responses from the COVID-19 Cannabis Health Study, a cross-sectional online survey administered via REDCap between March 2020 and March 2022. All respondents were cannabis consumers in the past year. Cannabis use patterns and chronic pain were self-reported via the COVID-19 Cannabis Health Questionnaire. Statistical analysis included Chi-square tests, Fisher’s exact tests, t-tests, and multivariable logistic regression with a two-tailed alpha of 0.05 for significance.

Results: Among 2243 participants, 50.3% consumed cannabis to manage chronic pain. Younger age (< 40 years; aOR: 3.20, 95% CI: 2.59-3.96), Hispanic/Latino ethnicity (aOR: 2.20, 95% CI: 1.56-3.05), and higher income levels (> $100,000 annually; aOR: 1.69, 95% CI: 1.25-2.29) were associated with higher odds of consuming cannabis to manage chronic pain. Participants using cannabis for chronic pain were more likely to use a CBD/THC ratio. The pandemic led to increased dosages and changes in consumption methods: 40.5% increased their cannabis dose, smoking as the primary method declined from 62.2% before the pandemic to 34.5% afterward, while edibles rose from 7.9% to 30.9%, and tinctures from 3.2% to 8.6%. Route changes varied with chronic pain status.

Conclusion: There was a shift from smoking to nonsmoking methods to manage chronic pain. Those who were younger and those of Hispanic/Latino ethnicity had higher odds of using cannabis for chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/41179652/

“In recent years, cannabis has emerged as a promising alternative for pain management, driven by increasing evidence of its analgesic properties.”

https://onlinelibrary.wiley.com/doi/10.1155/prm/9631487