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

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

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“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

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“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

Cannabidiol reduces atypical absence seizures and epileptic spasms in a Gabrb3+/D120N mouse model of Lennox-Gastaut syndrome

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“Objective: Lennox-Gastaut syndrome (LGS) is a drug-resistant developmental and epileptic encephalopathy (DEE). Preclinical drug development for LGS is constrained by a lack of syndrome-relevant animal models. We aimed to evaluate a Gabrb3+/D120N knock-in (KI) mouse model of LGS by quantifying atypical absence seizures and epileptic spasms and assessing their sensitivity to antiseizure agents.

Methods: Video-EEG recordings of adult (10-week-old) KI and wild-type (WT) littermates were scored for atypical absence seizures, and the acute effects of ethosuximide (200 mg/kg), ulixacaltamide (60 mg/kg), and cannabidiol (CBD, 100 mg/kg) on seizure incidence and duration were evaluated using a within-subjects, crossover design. Video recordings of postnatal day 16 (P16) KI and WT littermates were scored for epileptic spasms, and the effects of once-daily dosing with vigabatrin (100 mg/kg) and CBD (100 mg/kg) from P13 to P15 were evaluated against vehicle.

Results: Adult KI but not WT mice exhibited spontaneous atypical absence seizures. CBD, ethosuximide, and ulixacaltamide reduced seizure incidence and duration. Epileptic spasms were more frequent in KI than in WT mice at P16. CBD and vigabatrin significantly reduced spasm frequency compared to the vehicle.

Significance: Gabrb3+/D120N mice display robust atypical absence seizures and neonatal spasms that respond to antiseizure agents, supporting the predictive validity of this model as a preclinical platform for LGS drug discovery. CBD produced reductions in both atypical absence seizures and infantile spasms, suggesting that this model may be utilized as a translational tool for evaluating novel cannabinoid therapeutics for DEEs.

Plain language summary: Lennox-Gastaut syndrome (LGS) is a rare type of epilepsy that’s hard to treat and poses a challenge for developing new drugs. Finding suitable animal models that accurately represent LGS is crucial. This article describes the development of a mouse model of LGS with a genetic mutation that increases seizures and epileptic spasms. We tested how different antiseizure drugs affect the mice. CBD, ethosuximide, and ulixacaltamide reduced seizure incidence and duration. CBD and vigabatrin also reduced spasm frequency in young mice. These promising results suggest the mouse model could be a valuable tool for drug discovery in LGS.”

https://pubmed.ncbi.nlm.nih.gov/42274296

“We report for the first time that the clinically approved cannabinoid ASM CBD can reduce both atypical absence seizures and infantile spasms in the Gabrb3+/D120N mouse, providing a benchmark for future evaluation of cannabinoid therapies.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70289