Low doses of cannabis extract ameliorate non-motor symptoms of Parkinson’s disease patients: a case series

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“Introduction: Parkinson’s disease (PD) is mainly characterized by motor symptoms including muscle rigidity, resting tremor and bradykinesia. However, the management of the non-motor symptoms represent a relevant clinical challenger in PD. These non-motor symptoms include cognitive and sleep disturbance and there is evidence that cannabinoids may represent alternative and effective treatments for non-motor symptoms of PD.

Methods: Therefore, this study addressed the effects of oral treatment with cannabis extract on cognition, insomnia, and daytime sleepiness in six patients with moderate PD. The patients were randomized to receive two different doses of a cannabis extract: THC:CBD 250:28 μg/day (n = 3) or 1000:112 μg/day (n = 3). The assessment of cannabis administration related to the cognitive field was measured by the Montreal Cognitive Assessment test (MoCA test), the insomnia was assessed by the Insomnia Severity Index (ISI), and daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). All clinical evaluations were performed before treatment and at 15, 30, 60, and 90 days of treatment.

Results: The statistical analysis indicated a significant benefit of the cannabis extract treatment, at dose of 1000:112 μg/day after 60 days of treatment, on insomnia assessed by ISI. Moreover, the statistical analysis of data from ISI and MoCA tests showed a trend toward improvement over time, while no significant effect was observed in the ESS. There were no reports of significant adverse effects during the cannabis extract treatment.

Discussion: These results demonstrate benefits of short-time treatment (60 days) with low doses of cannabis extract on insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.”

https://pubmed.ncbi.nlm.nih.gov/40066073/

“In conclusion, these results demonstrate a possible benefit of short-time treatment (3 months) with low doses of cannabis extract on cognition and insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.”

https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1466438/full

Improvement in the Cognitive Function in Chronic Pain: Therapeutic Potential of the Endocannabinoid System

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“Chronic pain presents as a complex condition encompassing sensory (Zhang Z et al. Cell Rep 12;752-759, 2015) and emotional components, often accompanied by anxiety, depression, insomnia, and cognitive impairment. These factors significantly hinder daily activities and rehabilitation efforts.

The widespread prevalence of chronic pain imposes substantial clinical, societal, and economic burdens. While current analgesics have limitations and associated side effects such as tolerance, dependency, cognitive deficits, and a narrow therapeutic window, the search for new analgesic options remains imperative.

The endocannabinoid system (ECS), a key modulator in pain processing pathways, plays a crucial role in executive functions. This review specifically focuses on the cognitive impairments associated with chronic pain and highlights the pivotal role of the ECS in the cognitive aspects of pain. Additionally, the effectiveness of cannabinoid-based medications in improving executive functions in patients with chronic pain is evaluated.”

https://pubmed.ncbi.nlm.nih.gov/40059255/

https://link.springer.com/article/10.1007/s12035-025-04814-8

Spinal dorsal horn neurons involved in the alleviating effects of cannabinoid receptor agonists on neuropathic allodynia-like behaviors in rats

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“Mechanical allodynia, the pain caused by innocuous tactile stimuli, is a hallmark symptom of neuropathic pain that is often resistant to currently available treatments.

Cannabinoids are widely used for pain management; however, their therapeutic mechanisms for neuropathic mechanical allodynia remain unclear.

Using transgenic rats that enable to optogenetically stimulate touch-sensing Aβ fibers in the skin, we found that the intrathecal administration of the synthetic cannabinoid, WIN 55,212-2, alleviated the Aβ fiber-derived neuropathic allodynia. Furthermore, we injected adeno-associated virus vectors incorporating the rat cannabinoid receptor 1 (CB1 receptor) (encoded by Cnr1) promoter and tdTomato or short hairpin RNA targeting the CB1 receptor into the spinal dorsal horn (SDH) and demonstrated that the conditional knockdown of CB1 receptors in Cnr1+ SDH neurons attenuates the anti-allodynic effects of intrathecally administered WIN 55,212-2. Electrophysiological analysis revealed that Cnr1+ SDH neurons received excitatory synaptic inputs from the primary afferent Aβ fibers.

Collectively, our results suggest that the CB1 receptors in Cnr1+ SDH neurons are molecular and cellular targets of intrathecal WIN 55,212-2 to alleviate neuropathic allodynia.”

https://pubmed.ncbi.nlm.nih.gov/40058945/

https://linkinghub.elsevier.com/retrieve/pii/S1347861325000180

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

A Green Microwave-Assisted Extraction of Cannabis sativa L. Extract and Its Cytotoxic Activity Against Cancer Cells

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“Objectives: This study aimed to explore the use of D-limonene and some vegetable oils with different amounts of saturated and unsaturated fatty acids as alternative green solvents for microwave-assisted extraction (MAE) of cannabis (Cannabis sativa L.). A standardized cannabis extract was selected to evaluate its potential as a chemopreventive agent.

Materials and methods: Alternative green solvents, powder-to-solvent ratios, and irradiation cycles were determined to optimize the MAE conditions. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to assess the cytotoxic effects against human breast cancer (MCF-7), liver cancer (HepG2), and mammary epithelium (hTert-HME1) cell lines.

Results: The extracts obtained from D-limonene and palm oil contained the highest concentrations of cannabidiol (CBD) and D-tetrahydrocannabinol (THC). A standardized D-limonene extract of cannabis (DEC) containing 0.03% w/w CBD and 1.37% w/w THC was selected for the evaluation of cytotoxic activity compared with CBD and THC. The results revealed that CBD and THC exhibited significant cytotoxic effects (p<0.05) against MCF-7 and HepG2, with the 50% inhibitory concentration (IC50) values of 18.5 and 12.37 μg/mL for CBD and 24.21 and 4.30 μg/mL for THC, respectively, whereas DEC exhibited moderate cytotoxicity against MCF-7 (IC50 of 488.85 μg/mL). However, CBD and THC exhibited significant cytotoxicity (p<0.05) against hTert-HME1 (IC50 values of 35.61 and 25.63 μg/mL, respectively), whereas DEC exhibited low cytotoxicity against hTert-HME1 (IC50 of 1.537.03 μg/mL).

Conclusion: DECs containing appropriate levels of THC and CBD have the potential to be candidates for cancer treatment. However, further investigations are required to improve the efficacy and safety profiles.”

https://pubmed.ncbi.nlm.nih.gov/40052396/

“The present study identified D-limonene and palm oil as promising alternative green solvents for extracting cannabinoids from cannabis inflorescences under MAE optimal conditions. The MAE method offers several advantages, including reduced time and energy consumption. In this study, DEC exhibited moderate cytotoxicity against MCF-7 cells with higher selectivity than CBD and THC. Therefore, DEC containing an appropriate amount of THC and CBD may exhibit a more satisfying anticancer effect and be a promising candidate for cancer treatment. However, additional research is required to understand the mechanisms of anticancer activity and to investigate additional efficacy and safety profiles.”

https://www.turkjps.org/articles/a-green-microwave-assisted-extraction-of-c-lessemgreatersativalessemgreater-l-extract-and-its-cytotoxic-activity-against-cancer-cells/doi/tjps.galenos.2025.33490

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

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)”

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 aureusStreptococcus 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. aureusStr. 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