Exploratory Prospective Study of Self-Titrated Medical Cannabis for Nonmotor Symptoms in Parkinson’s Disease

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“Background: Medical cannabis (MC) has emerged as a potential therapy for Parkinson’s disease (PD), targeting motor and nonmotor symptoms (NMS), such as pain, sleep disturbance, and urinary dysfunction. Cannabinoid receptors in central and peripheral systems, including the bladder, provide a mechanistic basis for symptom modulation. This study evaluated the feasibility, safety, and preliminary clinical effects of MC on NMS in PD within a real-world, regulated framework.

Methods: In this single-center, open-label, prospective cohort, 68 patients with PD initiating MC were assessed at baseline and at 3 months using validated scales: the Non-Motor Symptoms Scale (NMSS), King’s Parkinson’s Disease Pain Scale (KPPS), PD Sleep Scale-2 (PDSS-2), PD Quality-of-Life Questionnaire-8 (PDQ-8), and International Prostate Symptom Score (IPSS), along with 2-day urinary diaries. Participants used either cannabis oil extract or inflorescence products with varying THC/CBD (Δ9-tetrahydrocannabinol/cannabidiol) ratios. Adverse events and withdrawals were recorded. Cannabinoid composition was analyzed via ultra-high-performance liquid chromatography and correlated with clinical outcomes.

Results: Fifty participants (mean age 65.6 ± 11.0 years; 68% male) completed follow-up. MC use was associated with improvements in NMSS total (Δ 14.5, p = 0.001), PDSS-2 (Δ 5.9, p < 0.001), KPPS (Δ 8.1, p = 0.004), PDQ-8 (Δ 1.5, p = 0.040), and the NMSS urinary domain (Δ 2.1, p = 0.050). Nighttime urinary frequency decreased (median Δ 0.5, p = 0.016), while daytime parameters were unchanged. No correlations were found between cannabinoid composition or THC/CBD enrichment type and clinical response. The dropout rate was 26.5%, mainly due to loss to follow-up.

Conclusions: Short-term, self-titrated MC was feasible and appeared generally well tolerated in this open-label setting, suggesting potential benefits for pain, sleep, and nocturnal urinary frequency in PD. These exploratory findings warrant randomized controlled trials focused on these domains and incorporating standardized dosing, pharmacokinetic monitoring, and predefined cognitive safety assessments to determine efficacy, safety, and optimal dosing.”

https://pubmed.ncbi.nlm.nih.gov/42304702

https://journals.sagepub.com/doi/10.1177/25785125261458680

Unexpected improvement of hyperhidrosis with cannabidiol

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“Hyperhidrosis is characterized by excessive sweating and it affects almost 5% of the population. The affected age group is wide, and it can affect from children to elderlies. There are two types of hyperhidrosis: generalized and focal. Treatment depends on the symptoms presented. In more severe cases, radiofrequency sympatholysis and bilateral thoracic sympathectomy are the options. However, recurrence is possible or the postoperative appearance of conditions called compensatory hyperhidrosis or reflex hyperhidrosis.

We describe two cases of patients treated with Cannabidiol who had significant and unexpected improvement of hyperhidrosis.

The first patient received Cannabidiol specific for public presentations at work, and the second patient had a diagnosis of autism spectrum disorder.

The hyperhidrosis improved in both patients immediately after using Cannabidiol.”

https://pubmed.ncbi.nlm.nih.gov/35170710

Don’t Sweat It: Cannabinoid CB1 Receptors Reduce Sweating in a Mouse Model

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“Numerous exocrine glands play key physiological roles in the body that include tearing, salivation, and lactation, as well as the control of body temperature via sweating. Malfunction of sweat glands can be deeply problematic or-in the case of anhidrosis-life-threatening. The prevalence of sweating disorders is high, affecting millions. The few available therapies are generally of limited effectiveness.

Several lines of evidence point to regulation of sweating by the cannabinoid signaling system, an arrangement that would mirror cannabinoid regulation of tearing and salivation.

Mice sweat in their paws via glands that closely resemble human eccrine sweat glands, including regulation by muscarinic signaling and by temperature. We applied a galvanic skin response-based assay to investigate cannabinoid regulation of sweating in awake, unanesthetized mice. The muscarinic agonist pilocarpine increased conductance while the antagonist glycopyrrolate reduced conductance, validating the model as a measure of sweating. The cannabinoid receptor agonist CP55940 substantially reduced conductance in wild-type and CB2 but not CB1 receptor knockout mice.

The phytocannabinoid tetrahydrocannabinol (THC) also reduced conductance, while the non-psychoactive cannabidiol (CBD) did not. Using immunohistochemistry, we detected CB1 receptors in periglandular cholinergic axons, the anandamide-synthesizing enzyme NAPE-PLD in myoepithelial cells, and the anandamide metabolizing enzyme FAAH in acinar cells. This indicates that a local CB1/anandamide-based circuit is present in mouse walking pads.

In summary, we employed a novel galvanic skin response-based assay to determine that cannabinoid CB1 receptors reduce sweating in a mouse model. This may point to a previously unappreciated effect on sweating in cannabis users.”

https://pubmed.ncbi.nlm.nih.gov/42287607

“In summary, we have made use of a galvanic skin response-based assay to measure the conductivity in the hind paws of awake, unanesthetized mice as a measure of sweating. We find the galvanic skin responses to be stable and consistent over time and, importantly, to be responsive to stimuli that increase or decrease basal sweating. Using this model, we determined that cannabinoid CB1 receptor activation reduces the galvanic skin response.

We propose that cannabinoid CB1 receptor activation reduces basal sweating in mice.

This effect may point the way to a new class of therapeutics for hyperhidrosis.”

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202601143R

Cannabinoids in hyperhidrosis

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“In our literature search for alternative treatments, we identified multiple unscientific and anecdotal sources claiming that cannabis can inhibit sweating. Our search of the medical literature revealed no evidence of a treatment attempt using cannabinoids, and thus, we initiated our study of one case with refractory generalized hyperhidrosis treated with cannabinoids from March to May 2021.

We observed a marked reduction in measured sweat and a significant improvement in the patient’s psychological well-being.

We conclude that, potentially, cannabinoids represent an effective therapeutic agent for hyperhidrosis and are worthy of further high-quality clinical investigation.”

“Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids.

We found a remarkable reduction in the volume of sweat and an improvement to the patient’s quality of life using this novel low-cost and low-impact approach.”

“In summary, we report a case of precisely analyzed effects of cannabinoid therapy in generalized hyperhidrosis.

We believe cannabinoids hold potential as a low side-effect and well-tolerated therapy, especially in refractory cases of hyperhidrosis.

This reflects not only in the reduced perspiration, but also in the significant improvement in the participant’s quality of life.”

https://pubmed.ncbi.nlm.nih.gov/36200741/

https://www.tandfonline.com/doi/full/10.1080/09546634.2022.2127308#d1e182

Protective effects of extracellular vesicle-like nanoparticles derived from Cannabis sativa adventitious roots against UVB-induced damage in human keratinocytes

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“Background: Plant-derived bioactive compounds are increasingly sought after in the cosmetics and pharmaceutical industries, prompting the development of sustainable production methods. This study explored the potential of Cannabis sativa adventitious root cultures to produce extracellular vesicle-like nanoparticles (CA-NPs) and investigated their protective effects against UVB-induced damage in human keratinocytes.

Methods: CA-NPs were isolated from Cannabis sativa root cultures and characterized for particle size, zeta potential and stability. HaCaT keratinocytes were used to assess the nanoparticles’ ability to improve cell viability, reduce apoptosis and alleviate oxidative stress after UVB exposure. Gene expression of skin barrier components and matrix metalloproteinases (MMPs) was analysed, and underlying signalling pathways (MAPK, Nrf2) were examined.

Results: CA-NPs (~128 nm, -12.9 mV) showed strong physicochemical stability and effectively protected HaCaT cells from UVB-induced damage. They suppressed MMP-1, MMP-3 and MMP-9 expression while enhancing skin barrier-related genes (HAS1, FLG, LOR, IVL). CA-NPs also modulated MAPK and Nrf2 pathways, reducing inflammation and boosting antioxidant defences.

Conclusion: Cannabis sativa-derived CA-NPs offer a promising natural approach to protect the skin from UVB-induced damage, supporting their potential as bioactive candidates for future skincare or cosmeceutical applications for preventing photoaging and inflammation.”

https://pubmed.ncbi.nlm.nih.gov/42298090

“These findings support the potential of CA-NPs as bioactive candidates for topical or cosmeceutical formulations aimed at alleviating UVB-induced skin damage and photoageing.”

https://onlinelibrary.wiley.com/doi/10.1111/ics.70108

Therapeutic potential of endocannabinoid system activation in opioid use disorder and pain

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“Introduction: Opioid use disorder (OUD) and chronic pain remain major global health challenges. Although opioid-based therapies provide effective analgesia, their long-term use is limited by safety concerns, dependence, and variable efficacy. Modulation of the endocannabinoid system (ECS) has emerged as a promising therapeutic strategy for pain management and opioid-related disorders.

Areas covered: This narrative review summarizes current evidence on ECS-targeted interventions for OUD, chronic non-cancer pain, and cancer-related pain. Relevant literature was identified through PubMed using search terms related to the ECS, cannabinoid receptors (CB1 and CB2), phytocannabinoids (Δ9 -tetrahydrocannabinol [THC] and cannabidiol [CBD]), synthetic cannabinoids, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors, and opioid – cannabinoid interactions. Particular emphasis is placed on mechanistic interactions between ECS and opioid signaling pathways, as well as evidence from preclinical and clinical studies evaluating therapeutic efficacy and safety.

Expert opinion: ECS modulation may alleviate pain, reduce opioid withdrawal symptoms, and improve affective outcomes. Interactions between cannabinoid and opioid receptors may produce synergistic analgesic effects while potentially mitigating opioid tolerance and dependence. However, clinical translation remains limited by small sample sizes, heterogeneous study populations, and variability in trial design. Well-controlled clinical trials are needed to establish optimal dosing strategies, evaluate long-term safety, and clarify the therapeutic role of ECS-targeted interventions in OUD and pain management.”

https://pubmed.ncbi.nlm.nih.gov/42295097

“The endocannabinoid system (ECS) represents a promising therapeutic target for opioid use disorder (OUD), chronic non-cancer pain, and cancer-related pain.”

“Cannabinoids (e.g., CBD and Δ9 -THC) exert analgesic and anti-inflammatory effects through CB1-mediated central mechanisms and CB2-mediated peripheral mechanisms.”

https://www.tandfonline.com/doi/full/10.1080/14728222.2026.2690138

Cannabidiol attenuates lung ischemia-reperfusion injury by modulating RIPK1/RIPK3-mediated necroptosis and HIF-1α/VEGF signaling

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“Objectives: Lung ischemia-reperfusion (IR) injury is a critical clinical condition characterized by oxidative stress, inflammation, and necroptosis, often leading to severe complications. Cannabidiol (CBD), a non-psychoactive cannabinoid, has demonstrated anti-oxidant and anti-inflammatory properties, but its role in modulating lung IR injury remains incompletely understood. This study investigated the protective effects of CBD on lung IR injury in rats, focusing on the RIPK1/RIPK3 necroptosis pathway and the HIF-1α/VEGF/eNOS signaling axis.

Materials and methods: Forty male Wistar albino rats were randomized into four groups: control, IR, IR+CBD (5 mg/kg), and CBD-only. Histopathological, immunohistochemical (TNF-α, Caspase-3), biochemical (TOS, TAS, OSI), and gene expression (RIPK1, RIPK3, HIF-1α, VEGF, eNOS) analyses were performed. The IR group exhibited significant oxidative stress, inflammation, and tissue damage, with elevated TNF-α, caspase-3, TOS, OSI, and necroptosis/apoptosis markers.

Results: CBD treatment markedly attenuated these effects, reducing oxidative stress (↑TAS, ↓TOS/OSI), suppressing inflammation (↓TNF-α), and inhibiting both apoptotic (↓Caspase-3) and necroptotic (↓RIPK1/RIPK3) pathways. Additionally, CBD down-regulated HIF-1α/VEGF/eNOS expression, suggesting modulation of hypoxia-responsive signaling.

Conclusion: These findings demonstrate that CBD mitigates lung IR injury by targeting oxidative stress, inflammation, and cell death mechanisms, highlighting its potential as a therapeutic agent. Further preclinical and clinical studies are warranted to validate these results.”

https://pubmed.ncbi.nlm.nih.gov/42291399

https://ijbms.mums.ac.ir/article_27571.html

Identification of cannabichromevarin as a potent stabilizer of the measles virus prefusion F protein: structural insights from long-timescale molecular dynamics

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“Measles virus (MeV) remains a serious public health concern, necessitating the development of effective antivirals targeting the viral fusion (F) glycoprotein.

This study employed a robust computational pipeline, including molecular docking, 1000 ns all-atom molecular dynamics (MD) simulations, and free energy landscape (FEL) analysis, to evaluate minor cannabinoids as novel inhibitors of the MeV F protein.

Initial virtual screening identified Cannabichromenic acid (CBCA), Cannabichromevarin (CBCV), and Cannabiripsol (CBR) as high-affinity leads, with docking scores of – 8.5, – 8.2, and – 8.1 kcal/mol, respectively, outperforming the reference inhibitor AS-48 (- 7.6 kcal/mol). Post-MD binding free energy calculations (MM-GBSA) further confirmed the thermodynamic superiority of CBCV (ΔGbind = – 44.7 kcal/mol) and CBCA (ΔGbind = – 30.1 kcal/mol) over the reference.

Dynamic analyses revealed that CBCV and CBCA effectively stabilize the F protein in its inactive prefusion conformation through a conformational locking mechanism. CBCV induced the most significant structural compaction (Rg = 2.4 nm) and displayed the sharpest global energy minimum (0.3 kcal/mol) in the FEL. Furthermore, ADMET profiling and ProTox-3.0 toxicity modeling identified CBCV as the most promising lead, possessing excellent drug-likeness, an inactive toxicity profile, and predicted blood-brain barrier permeability.

This work establishes minor cannabinoids as novel scaffolds for anti-MeV drug development, positioning CBCV as a strong candidate for treating systemic and neurological complications of measles, such as Subacute Sclerosing Panencephalitis.”

https://pubmed.ncbi.nlm.nih.gov/42286054

https://www.nature.com/articles/s41598-026-50199-6

“Cannabichromevarin (CBCV), also known as cannabivarichromene) is one of over 100 variants of cannabinoid chemical compounds that act on cannabinoid receptors. CBCV is a phytocannabinoid found naturally in cannabis, and is a propyl cannabinoid and an effective anticonvulsant and used to treat brain cancer and epilepsy“

Comparing cannabinoid extracts for treating cancer-related symptoms: a randomized placebo-controlled, triple-blind aggregate n-of-1 clinical trial

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“Context Despite widespread use of medical cannabinoids for cancer-related symptom management, systematic reviews consistently call for more clinical trial evidence.

Objectives This study aimed to determine and explore responses to medical cannabis extracts for cancer-related symptoms using patient-centred methodology.

Methods An aggregate N-of-1 study of clinically stable but symptomatic outpatients from 8 Canadian cancer centres, comparing three blinded sublingual extracts (THC; CBD; 1:1) with placebo, self-titrated within a prescribed schedule for four consecutive days each in randomized sequence for up to three cycles (total 16-48 days). The primary outcome was the frequency of at least a 1.4-point (20%) improvement in a 7-point Patient Global Impression of Change (PGIC) for at least one extract over placebo.

Results The primary outcome was achieved in 50/89 (56%) participants (p<0.001), with no significant preference of one extract over another on average, but a clear preference between extracts for most individuals. Changes in a modified Edmonton Symptom Assessment score and participant preference (n=91) confirmed these findings. Improved sleep, tiredness and anxiety contributed most to the overall improvement regardless of primary symptom. There were no demographic predictors of response. Mild adverse effects were common with all extracts including placebo but resolved rapidly on dose reduction/cessation. Moderate/severe adverse effects were rare but associated with THC.

Conclusions Medical cannabis extracts can be meaningfully beneficial for cancer-related symptoms in approximately 50% of patients, particularly for sleep and related symptoms. A starting dose of 2.5mg of THC/CBD three times a day was well-tolerated. Personalization of treatment is required to optimize response.

Key Messages Three cannabinoid extracts (THC; CBD; and 1:1) were significantly more effective than placebo based on a Patient Global Impression of Change, a modified Edmonton Symptom Assessment System and participant preference. The most helpful extract differed between individuals. Benefits were mostly in sleep, anxiety, and daytime tiredness irrespective of primary symptom.”

https://www.medrxiv.org/content/10.64898/2026.05.31.26354558v1

Acute Effects of Cannabinoid Combination Therapies in a Western Diet-Induced Murine Model of Metabolic Liver Disease

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“Pharmacological treatment of metabolic-dysfunction-associated steatohepatitis remains challenging due to its complex pathophysiology. The endocannabinoidome (eCB) has emerged as a promising therapeutic target given its central role in energy homeostasis and its pharmacological tractability. Western-style diets high in fat and sugar exacerbate metabolic liver disease, highlighting the need for effective interventions.

Here, we investigated the therapeutic potential of cannabinoid combinations targeting the eCB-liver axis in a Western diet-induced model of metabolic dysfunction.

Two weeks of treatment reduced body weight, improved glycaemic control, and ameliorated liver pathology. These effects were accompanied by decreased liver weight, improved liver enzyme profiles, and reduced histological features of steatosis and injury.

Overall, these findings suggest that modulation of the eCB system can induce acute improvements in metabolic and hepatic parameters under conditions of diet-induced metabolic stress. These results support further investigation into the eCB system as a therapeutic target, particularly to elucidate underlying mechanisms and longer-term effects.”

https://pubmed.ncbi.nlm.nih.gov/42278403

“To our knowledge, this is the first study to investigate the therapeutic effects of combination cannabinoid treatment in a mouse model of metabolic liver disease.

Targeting the endocannabinoid system, even acute treatment markedly improved metabolic parameters, including significant weight loss, reduced fasting blood glucose, and improved liver condition.

The triple cannabinoid combination produced the most pronounced effects, improving markers of hepatic injury and inflammation.

Mechanistically, modulation of the LPI/GPR55 and GPR119/incretin axes highlights the therapeutic potential of targeting the gut–liver axis using small-molecule agonists and endogenous bioactive lipids.”

https://www.mdpi.com/1422-0067/27/11/4872