Unexpected improvement of hyperhidrosis with cannabidiol

“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

“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

“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

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

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

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

“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

Chemical Characterization and Biological Potential of the Essential Oils from the Flowers of Two Cannabis sativa L. Cultivars from Komga, South Africa

Cannabis sativa L. is a medicinal plant cultivated globally due to its remarkable historical and scientific relevance. Through the consumption of its flowers, also referred to as inflorescences, which contain a high content of cannabinoids, terpenes and polyphenols, the therapeutic properties of C. sativa can be harnessed.

This study therefore aimed to determine the chemical profile, antioxidant and anti-inflammatory activities of the essential oils (EOs) obtained from the fresh and dried flowers of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, to assess which cultivar has greater biological potential.

The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while the in vitro antioxidant and anti-inflammatory activity of the EOs was analyzed using the DPPH and EAD methods, respectively. The identified constituents from the EOs were molecularly docked against NOX2 and NIK (NF-κB-inducing kinase) protein, which are implicated in oxidative stress. The afforded EOs were yellow (pale and bright yellow) in color with a sweet to mildly sweet aroma description.

A total of 51 constituents were identified in both fresh and dry oils from the Lifter cultivar, while the Cherrywine cultivar contained a total of 44 constituents. Eighteen compounds, were found to be the main chemical constituents consistent in the flower EOs of both cultivars, notably, caryophyllene (10.71-19.96%), levo-β-pinene (1.37-13.21%), humulene (5.88-9.77%), caryophyllene oxide (4.32-7.49%), D-limonene (1.40-5.48%), α-pinene (2.22-5.22%), nerolidol (0.63-4.97%), cis-β-ocimene (0.22-4.37%), linalool (1.12-4.28%), selina-3,7(11)-diene (0.15-4.23%), humulene-1,2-epoxide (1.23-3.32%), guaiol (0.17-2.60%), (+)-β-selinene (1.20-2.51%), trans-α-bergamotene (0.68-2.37%), β-ocimene (0.90-2.27%), fenchol exo- (0.15-1.27), terpineol (0.14-1.38%) and α-terpineol (0.19-0.75%). The fresh Lifter flower oil (LFO) showed 50% inhibition at 100 μg/mL, with an IC50 of 69.50 ± 4.05 µg/mL against DPPH, suggesting moderate to low radical scavenging activity. The maximum percentage inhibition response of DLFO, CFO and DCFO remained below 50% at all concentrations.

The antioxidant activity of fresh LFO may be attributed to its overall chemical composition. The flower oils showed in vitro inhibition of protein denaturation; however, the high standard deviation relative to the mean IC50 values limited the ability to rank the samples’ potencies. Further in silico studies on the putative constituents in the Lifter and Cherrywine cultivars revealed β-bisabolene and α-curcumene as potential molecular targets, with binding energy scores of -7.7 and -7.9 kcal/mol, respectively.

Thus, the study findings highlight the promising biological importance of C. sativa inflorescences in the management of oxidative stress-related conditions. Further studies may investigate the influence of environmental growing conditions on their chemical composition, total ROS analysis, pharmacokinetic properties, and in vivo efficacy against oxidative damage to DNA, proteins and lipids. Evaluating the toxicity of the flower EOs is also recommended.”

https://pubmed.ncbi.nlm.nih.gov/42280118

https://www.mdpi.com/1420-3049/31/11/1814


Cannabidiol corrects sleep deficits and reduces spontaneous seizures in Angelman syndrome model mice

“The off-label use of cannabidiol (CBD) has outpaced investigation. We assessed the effects of CBD in Angelman syndrome model mice lacking the Ube3a gene and found that chronic injection of CBD increased rapid-eye movement sleep during the dark cycle, restored “Siesta”, improved sleep homeostasis, and reduced spontaneous seizures following flurothyl kindling.”

https://pubmed.ncbi.nlm.nih.gov/42265437

“Cannabidiol (CBD), a major non-psychoactive and non-psychotomimetic phytocannabinoid constituent of cannabis, is gaining attention for its medical benefits. The multitarget and complex pharmacological nature of CBD in the central nervous system makes it a unique candidate for treating a wide range of complex neurological and psychiatric conditions, including seizures and sleep deficits.”

“This study primarily suggests that CBD restores REM sleep deficits in AS model mice. One hypothesis is that this effect may be related to CBD’s ability to enhance acetylcholine signaling, a central regulator of REM sleep. CBD’s ability to reduce the frequency of SRS, beyond its effects on induced-seizure suppression, further strengthens the preclinical evidence supporting its potential for clinical translation.” 

https://www.nature.com/articles/s41386-026-02462-7

Therapeutic Drug Monitoring of Cannabinoids: Therapeutic Reference Ranges for Delta-9-tetrahydrocannabinol in Medical Cannabis, Nabiximols, Dronabinol and Nabilone

“Medical cannabis, nabiximols, dronabinol and nabilone are used for various medical conditions.

Despite their pronounced pharmacokinetic variability and complex concentration-effect relationships, therapeutic drug monitoring recommendations are lacking. We aimed to identify therapeutic reference ranges based on blood concentration-clinical effect relationships. Studies reporting blood concentrations and clinical effects/adverse effects or assessing cannabinoid receptors 1 and 2 occupancy were selected through a systematic literature search in the MEDLINE database via PubMed. Twenty-three articles were selected for vaporized/smoked medical cannabis, three for nabiximols, nine for dronabinol and one for nabilone. No article was identified for delta-9-tetrahydrocannabinol-dominant cannabis extracts.

For vaporized/smoked medical cannabis, an orienting therapeutic reference range of 15-30 ng/mL delta-9-tetrahydrocannabinol was identified for pain reduction in diabetic peripheral neuropathy, while concentrations of <20 ng/mL delta-9-tetrahydrocannabinol were significantly correlated with intraocular pressure reduction and 7.5-10 ng/mL with improvement of tic symptoms. Half-maximum effective concentrations of 7-29 ng/mL delta-9-tetrahydrocannabinol were reported for “high” effects.

For nabiximols, a preliminary therapeutic reference range of 1-10 ng/mL delta-9-tetrahydrocannabinol was determined for treating neuropathic pain and spasticity in adults with multiple sclerosis. For chemotherapy-induced nausea and vomiting, a preliminary therapeutic reference range of 1-5 ng/mL for nabilone and 5-15 ng/mL delta-9-tetrahydrocannabinol for dronabinol was assessed.

In conclusion, relatively low concentrations may be sufficient to achieve therapeutic effects across all substances studied, with medical cannabis demonstrating these effects at lower concentrations than typically observed in recreational use. Nevertheless, adverse effects at therapeutic reference ranges cannot be excluded.”

https://pubmed.ncbi.nlm.nih.gov/42269696

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2853-4984

Endocannabinoid system and skeletal muscle health: insights from cannabidiol

“The endocannabinoid (EC) system is a complex network comprising endogenous ligands, enzymes responsible for their synthesis and degradation, and various receptors (including CB1 and CB2).

Present in many peripheral tissues, including skeletal muscle, EC system is now recognized to influence key physiological processes such as insulin sensitivity, mitochondrial metabolism, protein homeostasis and muscle development. Alterations in this system are associated with a variety of pathologies, including obesity, type 2 diabetes, sarcopenia, cachexia and muscle dystrophies.

In this context, cannabidiol (CBD), a phytocannabinoid devoid of psychoactive properties, is attracting growing interest as a potential therapeutic agent.

This article provides an analysis of the mechanisms by which the EC system, and more specifically the CB1 receptor, influences skeletal muscle development and function, while exploring emerging data on the potential benefits of CBD in various pathological conditions affecting skeletal muscle.”

https://pubmed.ncbi.nlm.nih.gov/42264146

“The endocannabinoid system (ECS) is composed of endogenous ligands (AEA, 2-AG), enzymes for their synthesis or degradation, and receptors (e.g., CB1, CB2). It also includes exogenous molecules like cannabidiol (CBD) produced from Cannabis sativa. Widely expressed in peripheral tissues such, the ECS plays a central role in the regulation of key skeletal muscle physiological processes, including insulin sensitivity, mitochondrial metabolism, protein homeostasis and skeletal muscle development.

Dysregulation of this system is associated with the development of metabolic and muscular disorders, such as obesity, type 2 diabetes, sarcopenia, cachexia and muscular dystrophies.

In this context, CBD, a non-psychoactive phytocannabinoid, has emerged as a potential therapeutic agent capable of modulating ECS activity, thereby contributing to the restoration of skeletal muscle function and homeostasis.”

https://www.sciencedirect.com/science/article/pii/S2212877826000803?via%3Dihub