Category Archives: Chronic Pain

Moroccan Cannabis sativa essential oil attenuates peripheral neuropathic pain induced by chronic sciatic nerve constriction injury in mice

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“Ethnopharmacological relevance: Cannabis sativa has been widely used in traditional medicine for its therapeutic properties. However, in Morocco, the ethnobotanical applications of Cannabis sativa, especially its essential oils, are underexplored. This study investigates, for the first time, the effects of Moroccan Cannabis sativa essential oil on peripheral neuropathic pain.

Materials and methods: Peripheral neuropathic pain was induced in mice through sciatic nerve injury. The mice were treated daily with cannabis essential oil for 21 days. Behavioral tests were conducted on days 1, 7, 14, and 21 to evaluate thermal, mechanical, and cold sensitivity. The essential oil’s chemical composition was analyzed using gas chromatography-mass spectrometry (GC/MS).

Results: The main constituents of the essential oil were (E)-caryophyllene (41.59%) and α-humulene (14%). Daily treatment with the essential oil significantly reduced pain sensitivity and improved functional and histological recovery over time. These effects are linked to the activity of the dominant terpenoids in the oil.

Conclusion: Moroccan Cannabis sativa essential oil shows significant therapeutic potential for managing peripheral neuropathic pain. By enhancing recovery and alleviating pain symptoms, it offers a promising alternative for treating chronic pain caused by nerve injuries.”

https://pubmed.ncbi.nlm.nih.gov/39947371/

“A multitude of recent studies have explored the broad biological properties of cannabis. Extracts from Cannabis sativa have demonstrated antimicrobial, anti-inflammatory, antinociceptive, and potent antioxidant activities.”

“This study examined the analgesic effects of terpenes found in Cannabis sativa essential oil on neuropathy. The results showed that chronic administration of these bioactive terpenes, specifically β-caryophyllene, α-humulene, and caryophyllene oxide, significantly increased pain sensitivity and response time in mice with neuropathy. Although morphine and THC-based treatments are commonly used to relieve neuropathic pain, these terpenes may offer a promising alternative with limited side effects. Clinical research has demonstrated the efficacy of cannabis-based treatments, leading several pain societies to recommend them for neuropathy management. “

https://www.sciencedirect.com/science/article/pii/S0378874125001692?via%3Dihub

The cannabinoid CB2 receptor mediates the analgesic effects of Cannabis sativa extract in a rat model of neuropathic pain

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“Neuropathic pain (NP) is a complex and debilitating condition that is often refractory to currently available analgesic medications.

Cannabis sativa extract (CSE) has been reported to exhibit analgesic properties across various pain models; however, the underlying mechanisms of action are not fully understood.

This study aimed to investigate the involvement of the cannabinoid CB2 receptor in mediating the analgesic effects of CSE in a rat model of NP, where NP was induced in male Wistar rats through chronic constriction injury (CCI) of the sciatic nerve.

Rats were randomly allocated into four groups: (1) Sham + vehicle, (2) CCI + vehicle, (3) CCI + CSE, and (4) CCI + CSE + AM630 (a CB2 receptor antagonist). CSE was administered intraperitoneally at a dosage of 30mg/kg once daily for 7 days, starting from day 7 to day 13 post-CCI surgery. To assess the involvement of the CB2 receptor, 7µg of AM630 was administered intrathecally to the rats in group 4, 30minutes before the CSE injections. Mechanical allodynia and thermal hyperalgesia were assessed using the von Frey filament and hot plate tests, respectively, at baseline (day 0) and on days 3, 7, 10, and 14 after surgery. Additionally, at the end of the study period (day 14), the expression level of Iba1 and GFAP genes was quantified in the lumbar enlargement tissues using real-time PCR.

The results demonstrated that CCI surgery induced mechanical allodynia and thermal hyperalgesia, along with the upregulation of Iba1 and GFAP genes in the vehicle-treated CCI group. Treatment with CSE significantly mitigated both allodynia and hyperalgesia and downregulated the expression of Iba1 and GFAP genes compared to the CCI + vehicle group. Furthermore, the administration of the CB2 receptor antagonist AM630 not only robustly blocked the antinociceptive effects of CSE but also reversed the significant downregulation of Iba1 and GFAP gene expression in the lumbar enlargement tissues.

These findings highlight the novel role of the CB2 receptor in mediating the analgesic effects of CSE, providing new insights into the potential therapeutic mechanisms of CSE in neuropathic pain management.”

https://pubmed.ncbi.nlm.nih.gov/39947333/

“In summary, this study provides evidence that CSE exerts analgesic and anti-inflammatory effects in NP through CB2 receptor activation. These findings contribute to the growing body of research supporting cannabinoids as potential therapeutic agents for NP management.”

https://www.sciencedirect.com/science/article/abs/pii/S0166432825000683?via%3Dihub

Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats

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“Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain.

Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration.

To this end, male and female rats were orally gavaged with cannabidiol (25 mg/kg), oxycodone (1.4 mg/kg), or a combination of both, after which they were tested in an operant thermal orofacial pain assay in which they voluntarily exposed their faces to cutaneous thermal pain to receive a palatable reward.

All three drug conditions produced analgesic effects of varying degrees, being most profound in the combination group where a statistically significant enhancement over oxycodone-induced analgesia alone was evident. Additionally, oxycodone administration decreased lick frequencies – a measure of motor coordination of rhythmic movements – which too was magnified by co-administration of cannabidiol.

Together these studies provide further support of an ability of cannabidiol to augment opioid effects, particularly analgesia, when administered by a route relevant to human pain management. As such, they encourage the notion that cannabidiol could find utility as an opioid-sparing approach to treating pain.”

https://pubmed.ncbi.nlm.nih.gov/39914591/

“Cannabidiol is an orally active constituent of the cannabis plant”

“Cannabidiol potentiates opioid analgesia in an operant orofacial pain assay in rats”

“Cannabidiol as an opioid-sparing approach to treating pain is worthy of more study”

https://www.sciencedirect.com/science/article/abs/pii/S0091305725000152?via%3Dihub

The comparative effectiveness of medicinal cannabis for chronic pain versus prescription medication treatment

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“Reviews of the effectiveness of medicinal cannabis for chronic pain vary in their conclusions. IASP has identified that a key missing evidence in this debate is data from observational cohort studies, analyzed with comparative effectiveness methods.

In a medically supervised context to the use of marijuana for chronic pain, we identified 440 patients certified for medical marijuana by pain specialists in a single healthcare system. They were characterized by a battery of patient-reported outcomes stored electronically in the University of Pittsburgh Patient Outcomes Repository for Treatment (PORT).

At 3 months, 38.6% were responders, based on clinically meaningful improvements in pain, function, or global impression of change, and maintained this response at 6 months. In the 157 patients who were coprescribed opioids, at 6 months there was a mean 39.3% decrease in morphine milligram equivalents (P < 0.05 for the difference vs baseline).

In addition, 8114 patients treated in the same pain clinics with prescription pain medications instead (nonopioid or opioid) during the same timeframe were selected from PORT as a control group for comparison. They had a 34.9% rate of response at 3 months. Using the causal inference method of stratified modeling, logistic regression revealed an odds ratio of 2.6 in favor of medical marijuana vs medication treatment (P < 0.01). Potential harms data were not available in the PORT registry.

Medical marijuana was comparatively more effective than prescription medications for the treatment of chronic pain at 3 months, although the populations compared were slightly different.”

https://pubmed.ncbi.nlm.nih.gov/39878633/

https://journals.lww.com/pain/abstract/9900/the_comparative_effectiveness_of_medicinal.807.aspx

Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids

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“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]

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“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

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“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

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“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

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“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

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“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