Author Archives: David

The Pharmacology of Cannabinoids in Chronic Pain

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“Background: Our objective was to provide an overview of the currently available scientific and clinical data supporting the use of Cannabis and Cannabis-derived products for the treatment of chronic pain disorders. We also provide information for researchers, clinicians, and patients to be better informed and understand the approach behind the recommendation of Cannabis as a potential adjuvant in the treatment/control of chronic pain. Cannabis and its bioactive compounds have sparked interest in the field of pain treatment in spite of its controversial history and status as a controlled substance in many countries. With the increase in chronic pain, physicians and patients have started to look at alternative ways to treat pain aside from traditional treatments. One alternative is the use of cannabis to reduce/treat chronic pain disorders based on anecdotal accounts and the function of its phytocannabinoids. The two main cannabinoids in cannabis, tetrahydrocannabinol (THC) and cannabidiol, act on CB1 and CB2 receptors (in addition to several additional receptors). It is through these pleiotropic receptor interactions that these compounds elicit their biological function including the reduction of chronic pain. In this narrative review, we included the most recent evidence supporting the use of cannabis in the treatment of chronic pain disorders including chronic neuropathic pain, cancer-induced neuropathic pain, chronic musculoskeletal pain, and chronic headaches and migraines.

Summary: Evidence suggests that cannabis and cannabinoids have an analgesic effect that arises from a combination of compounds and various receptor systems. These effects may be maximized with the use of a combination of cannabinoids. At the same time, the combination of cannabinoids helps minimize the undesirable side effects of some cannabinoids such as the psychoactivity of THC. With these findings, further research is necessary to assess the analgesic properties of other cannabinoids like cannabichromene and cannabigerol and their contributions to the reduction of pain.”

https://pubmed.ncbi.nlm.nih.gov/40046175/

“Cannabis sativa L. has been used as a medicinal remedy for thousands of years. It has gone through multiple periods of acceptance, dismissal/rejection, reacceptance, illegality and, most recently, rediscovery of its potential to address chronic medical conditions. In the last few decades, its recreational use has received growing acceptance, while its medical use has been encouraged in multiple jurisdictions. Most modern research has focused on the phytocannabinoids produced by the plant which have been found to help minimize chronic neuropathic pain and mitigate other disorders including seizure conditions (e.g., Lennox-Gastaut and Dravet syndromes) and spasticity in MS. This review has provided scientific evidence supporting the use of cannabis as an adjuvant in the treatment of chronic pain which could also lead pain reduction to the point of minimizing other pharmacological treatments.”

https://karger.com/mca/article/8/1/31/920366/The-Pharmacology-of-Cannabinoids-in-Chronic-Pain

“Designer cannabinoids could be the key to pain relief without adverse effects”

https://www.nature.com/articles/d41586-025-00546-w

A systematic study of molecular targets of cannabidiol in Alzheimer’s disease

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“Background: Alzheimer’s disease (AD) is a prevalent, incurable, and chronic neurodegenerative condition characterized by the accumulation of amyloid-β protein (Aβ), disrupting various bodily systems. Despite the lack of a cure, phenolic compounds like cannabidiol (CBD), a non-psychoactive component of cannabis, have emerged as potential therapeutic agents for AD.

Objective: This systematic review explores the impact of different types of cannabidiol on AD, unveiling their neuroprotective mechanisms.

Methods: The research used PubMed, Scopus, and Web of Science databases with keywords like “Alzheimer’s disease” and “Cannabidiol.” Studies were evaluated based on title, abstract, and relevance to treating AD with CBD. No restrictions on research type or publication year. Excluded were hypothesis papers, reviews, books, unavailable articles, etc.

Results: Microsoft Excel identified 551 articles, with 92 included in the study, but only 22 were thoroughly evaluated. In-vivo and in-silico studies indicate that CBD may disrupt Aβ42, reduce pro-inflammatory molecule release, prevent reactive oxygen species formation, inhibit lipid oxidation, and counteract Aβ-induced increases in intracellular calcium, thereby protecting neurons from apoptosis.

Conclusions: In summary, the study indicates that CBD and its analogs reduce the production of Aβ42. Overall, these findings support the potential of CBD in alleviating the underlying pathology and symptoms associated with AD, underscoring the crucial need for further rigorous scientific investigation to elucidate the therapeutic applications and mechanisms of CBD in AD.”

https://pubmed.ncbi.nlm.nih.gov/40034365/

“In conclusion, the finding of this study indicates that cannabidiol/derivatives inhibit AD progression through various mechanisms and key hypotheses regarding AD pathology. Nave CBD can reduce Aβ, IL-6 expression in peripheral leukocytes, and retarded cognitive decline. Compare with other CBD derivatives, CBD carbamate derivatives notably reduced Aβ1–42 levels, restored cognitive function to a normal state, and exhibited superior behavioral performance when compared to donepezil. CBD decreases Caspase 9, Caspase 3, and cleaved PARP1 protein levels and shows Antiapoptotic effects during cognitive decline. It also shows anti-cholinergic activity by inhibiting AChE and BuChE. As a result, the expression of ChAT can be normalized. In terms of the neuroinflammatory process, the expression of proinflammatory miRNAs (miR-146a, miR-155, and miR-34a) associated with TLR and NF-κB signaling is reduce. Therefore, continued research efforts should focus on elucidating the precise mechanisms of action, exploring potential synergies with other AD medications, and optimizing CBD formulations and derivatization to maximize therapeutic benefits in AD patients. These observations underscore the significance of further research and exploration into the therapeutic applications of CBD in the context of AD.”

https://journals.sagepub.com/doi/10.1177/25424823241284464

Chronic exposure to a synthetic cannabinoid improves cognition and increases locomotor activity in Tg4-42 Alzheimer’s disease mice

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“Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and behavior impairments. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease modifying and easily accessible therapies. Emerging evidence suggests that targeting the endocannabinoid system may hold promise for AD therapy as it plays a crucial role in different physiological processes, including learning, memory and anxiety, as well as inflammatory and immune responses.

Objective: In this study, we investigated the therapeutic potential of the synthetic cannabinoid WIN 55,212-2 on memory deficits in Tg4-42 transgenic mice.

Methods: Tg4-42 mice were assigned to two treatment groups to investigate the preventive effects of WIN 55,212-2 after a prolonged washout period, as well as the therapeutic effects of WIN 55,212-2 on behavior. Furthermore, the effects of WIN 55,212-2 treatment on AD pathology, including inflammation, amyloid-β load, neurogenesis, and brain glucose metabolism, were evaluated.

Results: Therapeutic WIN 55,212-2 treatment rescued recognition memory and spatial reference deficits in Tg4-42 mice. Furthermore, therapeutic WIN 55,212-2 administration improved motor performance. In addition, preventative WIN 55,212-2 treatment rescued spatial learning and reference memory deficits. Importantly, WIN 55,212-2 treatment did not affect anxiety-like behavior. However, therapeutic and preventative WIN 55,212-2 treatment resulted in an increase locomotor activity and swimming speed in Tg4-42 mice. WIN-treatment reduced microgliosis in the hippocampus of preventively treated mice and rescued brain glucose metabolism in therapeutically treated Tg4-42 mice.

Conclusions: Our findings emphasize the therapeutic promise of the synthetic cannabinoid WIN 55,212-2 in alleviating behavioral and cognitive deficits linked to AD.”

https://pubmed.ncbi.nlm.nih.gov/40034517/

https://journals.sagepub.com/doi/10.1177/25424823241306770

“WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC)”

Value of cannabidiol as adjunctive treatment for Lennox Gastaut syndrome: cost-effectiveness and budget impact analysis

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“Background: Lennox-Gastaut syndrome (LGS) is a severe encephalopathic disease that leads to a decrease in the quality of life, physical injury, psychosocial impairment, and a significant increase in treatment costs. Cannabidiol (CBD) is approved for the adjunctive treatment of tonic-colonic seizures in LGS. This study aimed to determine the cost-effectiveness of CBD compared to the usual treatment in patients with LGS syndrome.

Methods: We developed a lifetime-horizon Markov model to compare the cost-effectiveness of adjunctive CBD versus usual care. Additionally, we performed a budget impact analysis over a 5-year time horizon. The findings were presented as the incremental cost-effectiveness ratio (ICER) for CEA, with a willingness to pay threshold of $18,261 per QALY gained, and as the difference in the overall budget ($) between the scenarios with and without CBD for budget impact assessment.

Results: In the base case scenario, CBD was cost-effective compared with usual care $6573 per QALY. Sensitivity analyses substantiated these results. From a healthcare perspective, there is a 77% probability that CBD is cost-effective at a willingness to pay of $18,261 per quality-adjusted life-year (QALY). Overall, the market access of CBD was associated to an increased budget of about $3,459,846 (+ 33%) in the next 5 years simulated.

Conclusions: Compared to usual care, CBD seems to be cost-effective in LGS patients and sustainable, with less than 34% overall budget increased in the next 5 years. Future studies need to confirm our results in the real word setting and in other countries.”

https://pubmed.ncbi.nlm.nih.gov/40038638/

“Our study demonstrates that CBD is valuable as an add-on therapy for patients with LGS in Iran. At current list prices in Iran and assuming a WTP threshold of $18,261/QALY, CBD is cost-effective for the treatment of LGS. So CBD has a more advantage of efficacy compared with usual care and its incremental BI for health system is relatively acceptable. The present study also provides a reference for stakeholders to judge the value of cannabidiol.”

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-03972-9

A within-subject, double-blind, placebo-controlled randomized evaluation of the combined effects of cannabidiol and hydromorphone in a human laboratory pain model

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“Preclinical and epidemiological evidence supports that cannabinoids may have opioid-sparing properties and could be one strategy to decrease opioid use and associated harms like overdose and extramedical use.

The objective of this within subjects, double-blind, double-dummy, randomized human laboratory trial was to examine whether cannabidiol (CBD) increases opioid analgesic effects and whether there are corresponding increases in other opioid mediated effects.

Healthy participants (N = 31) attended 5 outpatient sessions where they received the following drug conditions: (1) placebo + placebo, (2) 4 mg hydromorphone + placebo, (3) 4 mg hydromorphone + 50 mg CBD, (4) 4 mg hydromorphone + 100 mg CBD, and (5) 4 mg hydromorphone + 200 mg CBD. Before and at multiple time points after drug administration, participants completed (1) quantitative sensory testing, which induced and assessed acute and chronic laboratory models of pain; (2) standard assessments, which queried acute subjective drug effects; and (3) tasks, which assessed psychomotor performance.

When combined with a dose of hydromorphone that did not reliably produce analgesic effects on its own, CBD increased the analgesic effects for some laboratory acute pain outcomes but none of the laboratory chronic pain outcomes. At the highest dose of CBD (200 mg), there were concurrent increases in self-report Bad Effects and adverse effects that were not observed at lower doses of CBD (50 mg). Cannabidiol mitigated psychomotor impairment observed with hydromorphone alone.

These findings suggest that lower doses of CBD (50 mg) may have utility for enhancing acute analgesic properties of opioids without having corresponding increases in bad effects.”

https://pubmed.ncbi.nlm.nih.gov/40035623/

https://journals.lww.com/pain/abstract/9900/a_within_subject,_double_blind,_placebo_controlled.840.aspx

Chronic Disease Symptoms Self-Managed by Cannabis During the COVID-19 Pandemic: Results from the COVID-19 Cannabis Health Study

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“Background: The COVID-19 pandemic has impacted billions of people worldwide, particularly those with chronic health conditions, and has been associated with increases in substance use, including cannabis. The purpose of this study was to estimate the prevalence of cannabis use for symptom management of chronic health conditions during the COVID-19 pandemic. 

Methods: The COVID-19 Cannabis Health Study is an ongoing study among adults ≥18 who self-report cannabis use. Analyses included 1,466 responses received between March 21, 2020, and March 23, 2022, from participants who self-reported cannabis use and a chronic health condition. We examined comorbidities, symptoms managed with cannabis during the COVID-19 pandemic, and fear regarding COVID-19 diagnosis and transmission using the COVID-19 Cannabis Health Questionnaire. Descriptive statistics, Chi-squared, and T-tests were conducted. Results were stratified by those who reported using cannabis to manage a chronic health condition (medicinal cannabis user, n = 1,333) and those who did not use cannabis to manage chronic health condition (non-medicinal cannabis user, n = 133). 

Results: Most (90.9%, n = 1,333) of the total sample (mean age: 47.1 years [standard deviations {SD} = 15.0]) reported using cannabis to manage a chronic health condition, of which 46.1% (n = 615) reported having a medical card/recommendation, and 4.6% received recommendations to use cannabis to manage COVID-19 from health professionals. There were significant differences in age, gender, race/ethnicity, and education by medicinal cannabis use status. Comorbidities prevalent among medicinal cannabis consumers were mental health-related (66.1%), pain (58.5%), cardiometabolic-related (30.5%), immune-related (21.9%), and respiratory-related (20.8%). The most reported symptoms self-managed with cannabis during the pandemic were sleep (69.2%), chronic noncancer pain (49.7%), acute pain (46.5%), headaches/migraines (39.0%), muscle spasms (33.6%), nausea/vomiting (30.6%), and appetite stimulant (29.9%). There were no statistical differences in COVID-19 testing, fear of diagnosis, fear of transmission, or isolation due to COVID-19 between medicinal and nonmedicinal cannabis consumers in this sample. 

Conclusions: The perceived therapeutic benefit of cannabis during the COVID-19 pandemic is evident by the high prevalence of adults who reported using cannabis for medicinal reasons despite no recommendation from their health provider. Research is necessary to understand the prospective impact of cannabis use for self-management of chronic disease, especially within the context of COVID-19.”

https://pubmed.ncbi.nlm.nih.gov/40008990/

https://www.liebertpub.com/doi/10.1089/can.2023.0234

Cannabis use and illicit opioid cessation among people who use drugs living with chronic pain

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“Introduction: Amidst the opioid overdose crisis, there is interest in cannabis use for pain management and harm reduction. We investigated the relationship between cannabis use and cessation of unregulated opioid use among people who use drugs (PWUD) living with chronic pain.

Method: Data for analyses were collected from three prospective cohort studies in Vancouver, Canada. All cohort participants who completed at least two study visits and reported both pain and unregulated opioid use in the past 6 months were included in the present study. We analysed the association between cannabis use frequency and opioid cessation rates using extended Cox regression models with time-updated covariates.

Results: Between June 2014 and May 2022, 2340 PWUD were initially recruited and of those 1242 PWUD reported chronic pain, use of unregulated opioids and completed at least two follow-up visits. Of these 1242 participants, 764 experienced a cessation event over 1038.2 person-years resulting in a cessation rate of 28.5 per 100 person-years (95% confidence interval [CI] 25.4-31.9). Daily cannabis use was positively associated with opioid cessation (adjusted hazard ratio 1.40, 95% CI 1.08-1.81; p = 0.011). In the sex-stratified sub-analyses, daily cannabis use was significantly associated with increased rates of opioid cessation among males (adjusted hazard ratio 1.50, 95% CI 1.09-2.08; p = 0.014).

Discussion and conclusions: Participants reporting daily cannabis use exhibited higher rates of cessation compared to less frequent users or non-users. Observed sex-specific differences in cannabis use and opioid cessation suggest potential differences in cannabis use behaviours and effects. Our findings add to the growing evidence supporting the potential benefits of cannabis use among PWUD, underlining the need for further research.”

https://pubmed.ncbi.nlm.nih.gov/40011075/

Pain Predicts Cannabis Initiation Among Emerging Adults: Results from the Population Assessment of Tobacco and Health (PATH) Study

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“Pain is highly prevalent among emerging adults (18-25 years old), and rates of cannabis use are increasing among this population. Research indicates pain is a unique risk factor and motivator for substance use. However, evidence for pain-cannabis use relations among emerging adults is largely cross-sectional, and the only prospective evidence focuses on the frequency, quantity, and consequences of cannabis use, not initiation.

Accordingly, this is the first study to examine pain as a prospective predictor of cannabis initiation among emerging adults.

Data were drawn from five annual waves of the Population Assessment of Tobacco and Health Study. Emerging adults who denied cannabis use at baseline (n = 4,185) were included in the analysis. At baseline, a tenth of emerging adults reported moderate/severe pain (≥4/10). Adjusted Cox regression analysis revealed that emerging adults with moderate/severe baseline pain were more likely to initiate cannabis use, and did so earlier over the subsequent 4 years, than those with no/low baseline pain.

These findings provide initial evidence for pain as a risk factor for cannabis initiation during emerging adulthood. Future research is needed to identify mechanisms by which pain motivates cannabis initiation and to examine the utility of pain-targeted content in cannabis use prevention and intervention efforts among emerging adults.”

https://pubmed.ncbi.nlm.nih.gov/40009033/

https://www.tandfonline.com/doi/full/10.1080/08964289.2025.2465525

Inhibitory Potential of Cannabis Biomass Extracts on Livestock-Associated Staphylococcal and Streptococcal Pathogens

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“Diseases caused by staphylococci and streptococci are a serious burden on livestock production, causing significant losses. In addition, the associated antibiotic resistance of these pathogens often makes treatment impossible or prolonged.

Cannabis sativa L. contains many compounds with antibacterial properties and shows great potential as a natural antimicrobial agent for agricultural use against both of these bacterial species.

The aim of this study was to compare the in vitro antibacterial activity of ethanol extracts from five cultivars of hemp, namely, Bialobrzeskie, Felina 32, Futura 75, mixed and Santhica 27, against Staphylococcus aureus, Streptococcus agalactiae and Streptococcus dysgalactiae.

All five cultivars exhibited a certain degree of inhibitory effect against all the pathogens tested with minimum inhibitory concentrations (MICs) ranging from 128 to 2048 μg/mL. The extract from the Santhica 27 cultivar was the most effective antibacterial agent with the lowest MIC value of 128 μg/mL against Str. agalactiae and two clinical isolates of S. aureus, followed by Bialobrzeskie and mixed cultivars with the same growth-inhibitory potential against Str. agalactiae.

The extracts from the Felina 32 and Futura 75 cultivars presented only weak activity with MIC values ranging from 256 to 2048 μg/mL. The extract from the Santhica 27 cultivar appears to be a promising product for future use in the treatment of staphylococcal and streptococcal infections in livestock.”

https://pubmed.ncbi.nlm.nih.gov/40005797/

“In this study, the antibacterial activity of ethanol extracts obtained from five different hemp cultivars (Felina 32, Futura 75, mixed, Santhica 27 and Bialobrzeskie) against various strains of S. aureus, Str. agalactiae and Str. dysgalactiae, including their antibiotic-resistant and antibiotic-sensitive forms, was investigated.

All five ethanol cannabis extracts possessed specific growth-inhibitory potential against the bacteria tested, while Santhica 27 was identified as the most effective cultivar followed by the mixed and Bialobrzeskie cultivars. In the case of the Felina 32 and Futura 75 cultivars, only weak antibacterial activity was observed.

In the context of ever-increasing bacterial resistance to antibiotics, it is necessary to find alternatives to antibiotic treatment, and cannabis has great potential in this area.”

https://www.mdpi.com/2076-2607/13/2/432

Cannabidiol (CBD) Acts as an Antioxidant on Gardnerella vaginalis, Resulting in Reduced Metabolic Activity, Loss of Survivability, and Elimination of Biofilms

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“Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an anti-inflammatory compound that also has antibacterial activities against several Gram-positive and certain Gram-negative bacteria. 

Objectives: Since G. vaginalis is an opportunistic pathogenic Gram-variable bacterium, we investigated its response to CBD. 

Methods: The antibacterial activity of CBD was studied by broth dilution assay, changes in intracellular ATP levels, and the ability of bacteria to recover on chocolate agar plates. The antibiofilm activity was investigated by MTT metabolic assay, crystal violet staining, and HR-SEM. Flow cytometric analyses were performed to measure changes in membrane potential, membrane perforation, and metabolic activity. Reactive oxygen species (ROS) production was analyzed using the nitro blue tetrazolium (NBT) reagent. Gene expression was determined by semi-quantitative real-time PCR, while protein composition was determined by LC-MS/MS analysis. 

Results: We observed that G. vaginalis clinical isolates exhibited high susceptibility to CBD with a minimum inhibitory concentration (MIC) of 2.5 µg/mL CBD. CBD induced rapid membrane hyperpolarization and caused cytoplasmic leakage of ATP without increasing propidium iodide uptake. This was accompanied by reduced metabolic activity and loss of survivability. Proteomic analysis revealed decreased expression of some ribosomal-associated proteins. CBD exhibited antioxidant activity by reducing intracellular ROS levels in a dose-dependent manner. The antibacterial effect was neutralized by the free radical scavenger α-tocopherol, suggesting the involvement of radicals in executing the antibacterial effect. Importantly, CBD not only prevented the biofilm formation of G. vaginalis but also reduced the metabolic activity and biofilm biomass of preformed, mature biofilms. Real-time PCR analysis of G. vaginalis treated with CBD for 6 h showed an increase in the expression of biofilm-associated genes, suggesting that the antibiofilm activity of CBD is mainly due to its antibacterial effect. CBD did not alter the ability of G. vaginalis to adhere to HeLa cervical carcinoma cells and CBD-treated bacteria were still phagocytosed by RAW264.7 macrophages. 

Conclusions: Our study shows that CBD exhibits antibacterial and antibiofilm activities against G. vaginalis clinical isolates and is thus a potential drug for the treatment of vaginosis caused by this bacterium.”

https://pubmed.ncbi.nlm.nih.gov/40001381/

https://www.mdpi.com/2079-6382/14/2/136