Category Archives: Pain

Entourage effects of nonpsychotropic cannabinoids on visceral sensitivity in experimental colitis

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“Abdominal pain is the most disabling symptom of inflammatory bowel diseases, but current treatments are limited, leading patients to seek alternatives such as cannabis.

Cannabis contains over 100 cannabinoids which, unlike tetrahydrocannabinol, are biologically active compounds often without psychotropic effects (ie, nonpsychotropic cannabinoids [npCBs]). These npCBs have analgesic and anti-inflammatory properties and may show potentiating effects when administered in combination, referred to as the entourage effect.

Here, we investigated the analgesic effects of cannabichromene, cannabidiol (CBD), cannabidivarin, and cannabigerol (CBG), individually and in combination, using the mouse model of dextran sulfate sodium colitis-induced visceral hypersensitivity (VHS).

We then explored antinociceptive targets through patch-clamp electrophysiology on dorsal root ganglia neurons and recombinant channels. We found that a single injection of 10 mg/kg of either CBD or CBG reduced both VHS and c-Fos activation in the spinal dorsal horn. Moreover, a combination of npCBs consisting of 5 mg/kg CBD with 1 mg/kg of cannabichromene, cannabidivarin, and CBG-all at subtherapeutic dosages-reduced VHS, without altering colitis. Electrophysiological recordings revealed that the antinociceptive mixture of npCBs acts through voltage-gated sodium and calcium channels, particularly Cav2.2, but not Cav3.2 and Kv channels.

These results suggest that CBD, CBG, and a mixture of npCBs given at subtherapeutic doses may be beneficial in managing VHS associated with inflammatory bowel disease.

SIGNIFICANCE STATEMENT: Cannabis is increasingly used as an alternative treatment for managing pain associated with chronic conditions. Nonpsychotropic cannabinoids, such as cannabidiol, interact with ionotropic and voltage-gated ion channels. In our study, we demonstrated that cannabidiol, cannabigerol, and a combination of nonpsychotropic cannabinoids, administered at subtherapeutic doses, effectively alleviated visceral hypersensitivity associated with inflammatory bowel disease.”

https://pubmed.ncbi.nlm.nih.gov/39921943/

https://jpet.aspetjournals.org/article/S0022-3565(25)09725-3/abstract

UK Medical Cannabis Registry: An Analysis of Clinical Outcomes of Medicinal Cannabis Therapy for Cancer Pain

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“Cancer pain (CP) is a prevalent condition with limited pharmacotherapeutic options. Cannabis-based medicinal products (CBMPs) have shown analgesic effects, but their efficacy in CP remains contentious.

This study aims to evaluate the change in patient-reported outcome measures (PROMs) and adverse events (AEs) in CP patients treated with CBMPs.

A case series was conducted using prospectively collected clinical data from the UK Medical Cannabis Registry. Primary outcomes were the changes in the Brief Pain Inventory (BPI), pain visual analogue scale (Pain-VAS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7), Patient Global Impression of Change (PGIC) and Single-Item Sleep Quality Scale (SQS) questionnaires from baseline to 1, 3, and 6 months. AEs were recorded and graded. p < 0.050 was considered statistically significant. One hundred and sixty-eight participants were included.

CBMPs were associated with improvements in all pain-specific PROMs at all follow-up periods (p < 0.050).

Improvements in GAD-7, SQS, and EQ-5D-5L index scores were also observed (p < 0.050). Twenty-nine AEs (17.26%) were reported by five patients (2.98%), mostly mild-to-moderate (72.41%). Although the observational design means causality cannot be established, the findings support the development of future randomized controlled trials into CP management with CBMPs.”

https://pubmed.ncbi.nlm.nih.gov/39921589/

“This study found that initiation of CBMPs is associated with improvements in pain-specific and general health-related quality of life outcomes in CP patients over six months, with a relatively low incidence of mild-to-moderate AEs and no life-threatening AEs.”

https://www.tandfonline.com/doi/full/10.1080/15360288.2025.2457101

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

Medicinal Cannabis and the Intestinal Microbiome

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“Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries.

The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea.

It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut-microbiota-brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems.

An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity.

This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota.

We advance an exogenous cannabinoid-intestinal microbiota-endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis.”

https://pubmed.ncbi.nlm.nih.gov/39770543/

“Furthermore, other modes of delivery of medicinal cannabis, such as oro-buccal, sublingual and inhaled/smoked alternatives, provide cannabinoids that have rapid access to the systemic circulation, bypassing the intestinal tract.”

https://www.mdpi.com/1424-8247/17/12/1702

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