“The endocannabinoid system (ECS) is a complex signaling network essential for regulating various physiological processes in the body. Selective cannabinoid receptor ligands have been developed to modulate specific ECS signaling pathways, offering potential therapeutic benefits. These ligands, with high selectivity and affinity for cannabinoid receptors, demonstrate potential in managing diverse medical conditions. Standardizing dosing is crucial to ensure reliable therapeutic effects, as cannabinoids may exhibit biphasic effects. Combination strategies involving both CB1 and CB2 receptor modulation show promise in managing complex conditions, including chronic pain, autoimmune disorders, and neurodegenerative diseases.”
“Introduction: Chronic pain remains a challenge, with standard therapies often providing inadequate pain relief and causing undesirable side effects. Medicinal cannabis has emerged as promising alternative. This study assessed the impact of a cannabis hybrid extract on pain intensity and quality of life in daily clinical use.
Methods: ESCAPE was an observational study and included patients aged ≥ 18 years with chronic pain in Germany. The primary objective was to evaluate the effectiveness of the Cannamedical® Hybrid Cannabis Extract THC25:CBD25 on pain during four visits (V1-V4) in clinical practice, and key secondary objectives were pain interference and quality of life. Pain intensity was measured using the Numeric Rating Scale (NRS) of the Brief Pain Inventory (BPI) questionnaire. Pain interference was evaluated with the BPI pain interference subscore, and quality of life-particularly physical and mental health-was assessed with the Short Form-12 (SF-12) questionnaire. Additionally, patient and physician satisfaction with the extract was assessed.
Results: The study included 64 patients (50% female) with chronic pain (intention-to treat population; ITT). Cannabis-naïve patients of the ITT were defined as a subgroup and analyzed separately (N = 35). Mean (± SD) NRS-assessed pain intensity decreased during the study, in both the ITT (5.46 ± 1.73 at V1 vs. 3.37 ± 2.43 at V4) and in the cannabis-naïve subgroup (5.92 ± 1.34 at V1 vs. 2.37 ± 1.69 at V4). Mean pain interference subscore decreased between V1 and V4 for the ITT (5.39 ± 1.92 vs. 3.38 ± 2.46) and the cannabis-naïve group (5.68 ± 1.46 vs. 2.54 ± 1.99). Physical and mental health improved in both groups and high satisfaction with the hybrid cannabis extract was reported by patients and physicians.
Conclusion: Treatment with the Cannamedical® Hybrid Cannabis Extract THC25:CBD25 in daily clinical practice showed positive effects on patients’ pain and quality of life.”
“The aim of this work was to assess the effectiveness of full-spectrum cannabis (THC and CBD) extracts as adjuvants in the treatment of chronic pain. This is a prospective, open label, longitudinal study.
Major cannabinoids were analyzed in herbal preparations using high performance liquid chromatography (HPLC). Subjects were included when chronic pain diagnosis criteria was met according to physicians’ diagnosis. A patient stratification protocol was developed using a visual analogue scale to measure pain, a numerical scale for life quality parameters and a self-administered health survey. Eighty-eight patients aged between 35 and 88 years were included.
A significant decrease in both pain and other life quality parameters was observed between time zero and subsequent time intervals, excepting the “appetite” variable.
Overall, 51 individuals reported a decrease in pain, 38 a decrease in anxiety and 48 in insomnia, with “decrease” defined as symptom reduction of 50% or more between the first and last consultation. In addition, 23 subjects reduced or discontinued other analgesics and/or anti-inflammatory drugs during the trial. Adverse effects were mild and reversible.
These results are consistent with previous studies, supporting effectiveness and safety of cannabis extracts as adjuvants in the treatment of chronic pain.”
“Background: Medical cannabis (MC) is being used with greater frequency in the management of chronic pain. While its efficacy in pain relief is promising, questions about patterns of use and efficacy warrant further investigation. This study aimed to evaluate long-term MC use patterns, perceived efficacy, and its impact on cognition among patients with chronic musculoskeletal noncancer pain.
Methods: This prospective study included patients who were certified for MC between October 2022 and December 2024. Patients who were certified for MC under Pennsylvania state guidelines for a minimum of one year were tracked, yielding 129 patients for analysis. The patients completed an Inventory of Medical Cannabis Use (IMCU) questionnaire assessing usage patterns, dosage knowledge, efficacy, cognitive effects, and tolerance changes. The responses were collected in a password-protected database.
Results: A total of 77.5% of patients reported using MC daily or near daily. Topical formulations were most frequently used (63.6%). Approximately half of the respondents were uncertain of their exact tetrahydrocannabinol/cannabidiol (THC/CBD) dosage, with a median oral dose of 10 mg recorded among those who provided estimates. High levels of perceived efficacy were reported, with over 93% of respondents agreeing or strongly agreeing that MC improved their primary symptoms. Cognitive and motor effects were minimal for most users, with 72.1% reporting no impact. Furthermore, 79.8% of respondents indicated stable usage patterns over the prior three months, and very few reported a need or external suggestion to reduce MC intake.
Conclusions: Long-term MC use is a stable and well-tolerated option for managing chronic musculoskeletal pain, with high patient-reported efficacy and minimal cognitive impact. These findings support its role in pain management while highlighting the need for further research on optimal dosing and long-term safety.”
“Inflammation is the organism’s protective mechanism to restore cellular and tissue homeostasis. Cannabidiol has been reported for its ability to bind to diverse receptors related to or not related to the endocannabinoid system, with good safety being one of the most promising phytocannabinoids for therapeutical purposes. CBD has shown in vitro and in vivo ability to significantly reduce the production of cytokines and other inflammatory mediators, with an unclear mechanism of action.
Herein, we report the design and synthesis of a novel series of eight terpene N-acylaryl hydrazone analogues and their pharmacological evaluation for potential antioxidant, antinociceptive, and anti-inflammatory properties.
Our results led to the identification of compounds 5a (PQM-242), with significant peripheral and central antinociceptive effects, 5b (PQM-243), and 5g (PQM-248) with antinociceptive activities probably related to the ability of modulation of TRPV1 receptors, and 5c (PQM-244) that seems to have the most promising peripheral antinociceptive profile, showing significant effects on both neurogenic and inflammatory phases of formalin-induced licking test, coupled to potential antioxidant activity.
Overall, our experimental data suggest that the new CBD-based architecture is capable of ensuring peripheral and central antinociceptive effects by different modes of action, with no in vivo toxicity and adequate predicted ADME properties.”
“Introduction: As opioid-related drug overdoses remain a public health crisis, there is a critical need for innovative approaches to developing safer analgesics with improved safety profiles. BDH-001 is a fixed-dose combination of low-dose buprenorphine (BUP) and cannabidiol (CBD) being developed as a safer analgesic than currently available opioids. The purpose of this study was to examine the analgesic and opioid-sparing effects of BDH-001 and to complete an in vivo safety assessment in rats.
Methods: Analgesic effect of BDH-001 was assessed using the chronic constriction injury model of chronic neuropathic pain with pain threshold assessed via Von Frey testing. Drug-drug interaction effects on pharmacokinetic (PK) parameters were assessed in a single dose PK study in rodents. The effects on respiratory depression were also assessed and confirmed in two separate rodent studies performing blood gas analysis and measuring O2 saturation.
Results: BDH-001 (combination of subanalgesic BUP dose and CBD) resulted in statistically significant increases in pain threshold compared to saline (p < 0.001), CBD alone (p < 0.01), and BUP alone (p < 0.05). The half-life of BUP was significantly shorter in the presence of CBD compared to BUP alone (p = 0.008), with no significant changes in any other BUP pharmacokinetic parameter assessed. CBD was found to attenuate BUP-induced respiratory depression in rats when assessing blood gases (p < 0.05) and O2 saturation (p < 0.05) over several time bins.
Conclusions: Data obtained in the present study indicate the addition of CBD to BUP was opioid-sparing and attenuated BUP- but not morphine-induced respiratory depression. There was no evidence these findings were the result of a PK interaction. Results support the hypothesis that BDH-001, a fixed-dose combination of BUP and CBD, may provide effective analgesia with a more favorable safety profile.”
“Buprenorphine is a medication that plays a crucial role in treating opioid use disorder (OUD), also known as opioid addiction. It works by partially activating the same receptors in the brain as opioids, helping to reduce withdrawal symptoms and cravings without producing the intense euphoria or dangerous side effects associated with full opioid agonists like heroin or fentanyl.”
“Cannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects.
This study aimed to encapsulate cannabigerolic acid (CBGA) in poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) and investigate the effects of combining CBGA NPs with cannabis-derived terpene-loaded NPs (myrcene [MC], nerolidol [NL], and caryophyllene [CPh]) for potential applications in pain management.
CBGA NPs (152 nm) and terpene-loaded NPs (233-297 nm) were prepared via nanoprecipitation and emulsion-solvent evaporation, respectively, exhibiting a polydispersity index < 0.3 and negative zeta potentials (-23 to -26 mV). Encapsulation efficiency was 98.6 % for CBGA and 13-33 % for terpenes. CBGA release followed a biphasic profile, with ∼ 20 % released within 4 h and sustained release over 72 h. In vitro evaluation used HEK293 cells expressing the nociceptive transient receptor potential vanilloid-1 (TRPV1) channel, a key mediator of pain perception. TRPV1 activation was assessed via calcium influx kinetics (Fluo-4 indicator). The EC50 values were 23.8 µg/mL (CBGA NPs), 8.0 µg/mL (MC NPs), 6.7 µg/mL (NL NPs), and 13.3 µg/mL (CPh NPs). Combinatorial treatments of CBGA NPs with terpene NPs at their respective EC50 concentrations revealed significantly enhanced calcium influx compared to individual NPs, with the strongest interaction observed for CBGA/NL and moderate effects for CBGA/MC. Fluorescence imaging further corroborated these findings.
These results suggest that combining CBGA NPs with terpene-loaded NPs could potentiate pain-relief efficacy, offering a promising strategy for advanced therapeutic formulations.”
“Objectives: Current pharmacological treatments for neuropathic pain have limited efficacy and may cause undesirable side effects. Cannabidiol (CBD)-enriched cannabis oil and omega-3 fatty acids (ω-3) have emerged as potential therapeutic options due to their analgesic and anti-inflammatory properties. This study aimed to assess the antinociceptive effects of combining CBD-enriched cannabis oil and ω-3 in rat models of acute and neuropathic pain.
Methods: Using the hot plate test for acute pain and the chronic constriction injury (CCI) model for neuropathic pain, thermal and mechanical hypersensitivity were evaluated. Additionally, walking track analysis and the rotarod test assessed functional recovery of the sciatic nerve. Beyond that, the histological analysis of sciatic nerves exposed the neuropathological findings of the treatments.
Key findings: The combined treatment of CBD-enriched cannabis oil and ω-3 effectively prevented thermal and mechanical hypersensitivity, while also improving motor impairment-induced peripheral neuropathy. Finally, combination treatment showed a protective effect against degeneration resulting from CCI.
Conclusions: These findings underscore the potential of CBD-enriched cannabis oil and ω-3 as a novel therapeutic approach for neuropathic pain management, offering promising implications for future research and clinical practice.”
“Background and aim: Use of potent painkillers like opiates are limited by their abuse potential and adverse physiological effects necessitating new therapeutics for pain management. This study assessed the efficacy of oral cannabinoid formulations (F1-F4) in alleviating chronic neuropathic pain (CP) and investigated their mechanisms through thermal algesia, inflammatory and oxidative stress biomarkers, and sensory nerve conduction velocity (SNCV).
Experimental procedures: A 21-day rat model of chronic constriction injury (CCI) of the sciatic nerve was used to evaluate the effects of oral cannabinoid formulations (F1: 500 mg, F2: 1000 mg, F3: 2000 mg, F4: 3000 mg) in MCT oil, with pregabalin as the reference. Male Wistar rats (35) were divided equally into seven groups, with all except the Sham group undergoing sciatic nerve ligation and receiving different formulations.On day 22, behavioral (hot plate, tail flick) and electrophysiological (sensory nerve conduction velocity, SNCV) assessments were performed. SNCV was also measured in the presence of CB1 and CB2 receptor antagonists. Additionally, blood-based markers of inflammation (TNF-α) and oxidative stress (MDA, GSH and CAT) were analysed.
Results and conclusions: The vehicle group exhibited significant hyperalgesia (p <0.005), reduced sensory nerve conduction velocity (SNCV) (p <0.005) and elevated MDA and TNF-α levels, along with decreased GSH and CAT levels in both serum and sciatic nerve tissue.Among the formulations, F2 significantly improved pain latency and SNCV (p <0.005) compared to the vehicle group and outperformed F1, F3, F4 and pregabalin (p <0.05). Its effects were mediated through CB1 and CB2 receptor agonism while simultaneously reducing oxidative stress and inflammation, highlighting its potential as a promising candidate for neuropathic pain management.”
“Cannabinoids, particularly cannabidiol (CBD) and tetrahydrocannabinol (THC), have been increasingly studied for their therapeutic applications in various medical fields. This systematic review aims to explore their role in oral surgery, focusing on pain management, inflammation control, and bone regeneration.
A systematic review was conducted using the PRISMA framework to identify relevant studies from the PubMed, Scopus, and Web of Science databases published up to November 2024. The review included clinical and preclinical studies investigating the effects of cannabinoids on orofacial pain, oral inflammation, and bone healing. Data on study design, cannabinoid types, and relevant outcomes were extracted and analyzed. CBD was the most commonly studied compound, with other studies evaluating CB1/CB2 receptor agonists, THC, and cannabis smoke.
Clinical trials showed mixed results: some studies found CBD effective in reducing dental or myofascial pain, while others found limited or non-superior outcomes compared to standard treatments (e.g., NSAIDs, corticosteroids). Among the four RCTs, three had a low risk of bias, and one moderate; all nine animal studies had a high risk of bias.
In conclusion, preclinical and clinical studies suggest that cannabinoids represent a promising non-opioid alternative for pain management and for oral inflammation.
Although some evidence suggests potential benefits of cannabinoids, particularly CBD, in oral health contexts, findings are derived from heterogeneous studies-many with high risk of bias. More high-quality, standardized clinical trials are necessary before recommending cannabinoids for routine dental practice.”
“Within the limitations of this review, cannabinoids—especially cannabidiol (CBD)—demonstrated potential in managing orofacial pain, reducing inflammation, and promoting bone healing.”
