Effect of a cannabidiol-based mouthwash on dental enamel properties and biofilm control: an In situ study

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“Objectives: This study evaluated the antibiofilm activity of experimental mouthwash containing different concentrations of cannabidiol (CBD) and the in situ effects on the physical and mechanical properties of dental enamel.

Methods: Bovine enamel fragments (6 × 6 × 2 mm) were mounted in intraoral appliances worn by 14 participants in a crossover design. Mouthwash containing CBD (0%, 0.01%, 0.05%, and 0.1%) and 0.12% chlorhexidine (CHX) were tested. Each experimental phase lasted 7 days, separated by washout periods. One side of the appliance was exposed to a cariogenic challenge (20% sucrose) prior to treatment. Surface roughness (Ra), microhardness (%KHN), and color change (ΔE00) were measured before and after treatments. Biofilm and yeast counts (log10 CFU) were quantified, and enamel surfaces were analyzed by scanning electron microscopy. Data were analyzed using two-way ANOVA with Bonferroni post hoc tests and Kruskal-Wallis with Dunn’s test (P < 0.05).

Results: Sucrose did not significantly affect Ra (P > 0.05), although CBD 0.1% showed higher roughness than CHX under sucrose exposure (P < 0.05). No significant differences in %KHN were observed among treatments; however, sucrose reduced microhardness in the placebo and CBD 0.01% groups (P < 0.05). CHX exhibited the highest ΔE00 values (P < 0.05). Biofilm formation was similar among CHX, CBD 0.05%, and CBD 0.1% (P > 0.05), while CHX showed lower yeast counts than CBD 0.01% and CBD 0.1% (P < 0.05).

Conclusion: CBD 0.05% demonstrated potential for biofilm control without adversely affecting enamel properties.

Clinical relevance: This study provides evidence supporting a natural compound-based mouthwash as a clinically viable alternative to chlorhexidine, showing similar efficacy and no associated adverse effects under the conditions tested.”

https://pubmed.ncbi.nlm.nih.gov/42380527

“Chlorhexidine digluconate (CHX) has been considered the gold standard mouthwash in dentistry for several decades. It is a cationic bisbiguanide with bacteriostatic activity at low concentrations and bactericidal effects at higher concentrations. However, its long-term use has been associated with several adverse effects, including taste alteration, tooth and tongue staining, oral mucosal irritation, parotid gland swelling, xerostomia, and the potential development of antimicrobial resistance.”

“Based on the findings of this study and considering its limitations, it can be concluded that cannabidiol-based mouthwashes were able to modulate dental biofilm formation in a concentration-dependent manner, with higher concentrations (0.05% and 0.1%) demonstrating performance similar to chlorhexidine in reducing biofilm accumulation, influencing its structural organization, and maintaining relative microhardness. This effect did not result in alterations to enamel surface topography. However, cannabidiol-based mouthwashes maintained color closer to acceptability thresholds.”

https://link.springer.com/article/10.1007/s00784-026-06985-7

Cannabinoids infused mouthwash products are as effective as chlorhexidine on inhibition of total-culturable bacterial content in dental plaque samples

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“Background: Dental plaque is a global health problem affecting people of various age groups. Cannabinoids are gaining enormous research attention due to its beneficial properties for various applications. A preliminary observation on antimicrobial property of cannabinoids against dental plaque bacteria has been reported recently. As a follow-up research, here we report the in vitro evaluation of cannabinoids infused mouthwash products against total culturable (aerobic) bacterial content from dental plaque samples.

Methods: We tested two cannabinoid-infused mouthwash products containing cannabidiol (CBD) and cannabigerol (CBG) respectively (each mouthwash containing < 1% cannabinoid by weight) in vitro against total-culturable bacteria from dental plaque samples collected from 72 adults aged between 18 and 83 years. The participants were grouped on the basis of Dutch periodontal screening index (DPSI) score. To compare the efficacy of our products, we included two most commonly available products over the counter (Product A and Product B) to represent commercially available mouthwash products and the gold standard chlorhexidine digluconate 0.2% as a positive control. The product A represents mouthwash containing essential oils and alcohol, and Product B represents alcohol-free mouthwash that contains fluoride. All the mouthwash products were evaluated directly as such without any dilution through disc diffusion and agar well diffusion approaches and the diameter of zone of inhibition was measured. The limitation in methodology was that, the samples were open-label and the person who performed the manual measurements was unblind to test and control products used.

Results: On average, the cannabinoids infused mouthwash products showed the similar bactericidal efficacy as that of chlorhexidine 0.2%. Both chlorhexidine 0.2% and cannabinoids infused mouthwash products were effective against all the samples tested. Product A did not show any significant antimicrobial activity in any of the samples tested, except that a very marginal inhibition with a zone of 7-8 mm was observed only in 9 samples. Product B did not show any detectable inhibition zone at all in any of the samples tested. The ranges of zones of inhibition (and their average) were 8-25 mm (18.1 mm) for CBD-mouthwash, 8-25 mm (17.7 mm) for CBG-mouthwash; 12-25 mm (16.8 mm) for chlorhexidine 0.2%; 0-8 mm (0.1 mm) for Product A; and 0 mm for Product B. Although the difference in performance was slightly higher than chlorhexidine in both the cases, the difference was statistically significant for CBD-mouthwash and near significant for CBG-mouthwash. No significant difference was observed between CBD- and CBG-mouthwash. No significant difference in performance was found between DPSI score groups for any of the product tested. To our knowledge this is the first report on such efficient mouthwash product with natural key ingredients including cannabinoids and without any kind of fluoride or alcohol.

Conclusions: Our in vitro results demonstrate the potential of cannabinoids in developing efficient and safer mouthwash products and next generation oral care products without fluoride and alcohol.”

https://pubmed.ncbi.nlm.nih.gov/33526124

“Cannabinoids (CBD / CBG) infused mouthwashes together with other natural key ingredients shows promising bactericidal activity in vitro against total-culturable aerobic bacterial content in dental plaque, with efficiency equivalent to or better than that of the gold standard (0.2% chlorhexidine). CannIBite mouthwash products with cannabinoids infusion offer a safer and effective alternative without any fluorides or alcohol. Based on our in vitro study, the cannabinoids infused CannIBite mouthwash products offer a much safer, efficient and natural alternative to alcohol and/or fluoride containing mouthwashes.”

https://link.springer.com/article/10.1186/s42238-020-00027-z

Tetrahydrocannabinol/cannabidiol in the treatment of restless legs syndrome

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“Background: Dopamine agonists were previously considered the first-line treatment for Restless Legs Syndrome (RLS); however, α2δ ligands are now recommended to prevent augmentation. As cannabinoids inhibit glutamate release in the striatum, they may represent an effective therapeutic option for RLS.

Objective: Evaluate the efficacy of 2.7 mg Δ9Tetrahyedrocannabinol/2.5 mg Cannabidiol (2.7mgTHC/2.5mgCBD) in RLS.

Methods: This is an exploratory, prospective, 3-month open-label trial. At baseline, patients underwent blood testing, respiratory polygraphy, and a 14-day actigraphy. Treatment was initiated at baseline, with dose titration at week 4 if required. The Expanded Disability Status Scale (EDSS), Epworth Sleepiness Scale (ESS), International Restless Legs Syndrome Rating Scale (IRLS), Modified Ashworth Scale, and EQ-5D were assessed at baseline and at weeks 4 and 12. The 14-day actigraphy was repeated at week 12. The primary endpoint was improvement in IRLS scores. Sleep parameters were evaluated as secondary endpoints. Primary end point: improvement in IRLS. Sleep parameters were secondary end points.

Results: Eighteen patients with RLS were included, of whom 16 had multiple sclerosis (MS). The cohort comprised 55.5% women, with a mean age of 51.87 years, a median EDSS score of 2, and a mean Ashworth score of 1 ± 1.19. Median iron metabolism parameters were within the normal range. At baseline, patients exhibited low daytime sleepiness (ESS: 10.63 ± 3.46) and severe RLS (IRLS: 22.44 ± 8.77). Mean sleep efficiency (SE) was 83.64 ± 6.03%, sleep latency (SL) was 26.71 ± 18.64 min, and wake after sleep onset (WASO) was 40.29 ± 10.03 min. IRLS scores improved significantly after both 1 month and 3 months of treatment (p < 0.001). WASO was significantly reduced (p = 0.015), whereas no significant changes were observed in SL or SE. After 1 year, 66.66% of patients remained on treatment and continued to show sustained improvement in IRLS scores (p = 0.000).

Conclusions: In this exploratory open-label study, treatment with 2.7 mg THC/2.5 mg CBD was effective in reducing RLS severity, as measured by the IRLS scale, in patients with MS and-associated idiopathic RLS. Improvements were observed after 1 and 3 months of treatment and were maintained after 1 year among patients who continued therapy.”

https://pubmed.ncbi.nlm.nih.gov/42387200

https://link.springer.com/article/10.1007/s00415-026-13975-y

Cannabidiol in the anterior insular cortex attenuates chronic neuropathic pain and comorbid anxiety- and depression-like behaviors: involvement of CB1 and 5-HT1A receptor signaling

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Background: Chronic neuropathic pain (NP) is frequently accompanied by anxiety- and depression‑like symptoms, reflecting maladaptive interactions between nociceptive and affective brain networks. The anterior insular cortex (AIC) integrates sensory and emotional dimensions of pain and represents a potential target for pharmacological modulation. Cannabidiol (CBD) exhibits analgesic and anxiolytic/antidepressant‑like properties through interactions with endocannabinoid and serotonergic systems.

Objectives: We investigated whether CBD microinjection into the AIC modulates NP and its affective comorbidities, and whether these effects depend on CB1 and 5‑HT1A receptors.

Methods: Male Wistar rats were subjected to chronic constriction injury (CCI) of the sciatic nerve. Fourteen days later, guide cannulae were implanted into the AIC. On day 21 post‑CCI, animals received intra‑AIC microinjections of CBD (15, 30, or 60 nmol/200 nL) or vehicle. Mechanical (von Frey test) and cold (acetone test) allodynia, anxiety‑like behavior (open field and elevated plus maze tests), and depression‑like behavior (forced swim and sucrose spray tests) were assessed by different psychobiological tests. The role of cannabinoid and serotonergic receptors was addressed by intra‑AIC pretreatment with either the CB1 receptor antagonist AM251 or the 5‑HT1A receptor antagonist WAY-100,635 in independent groups.

Results: AIC pretreatment with CBD dose‑dependently reduced mechanical and cold allodynia and anxiety‑ and depression‑like behaviors, with the most robust effects observed at 60 nmol. AIC Pretreatment with either AM251 or WAY-100,635 abolished the antinociceptive and affective effects of CBD.

Conclusion: CBD administration within the AIC produces integrated analgesic, anxiolytic, and antidepressant-like effects in a model of neuropathic pain. These effects are consistent with the involvement of CB1 and 5-HT1A receptor signaling. The findings identify the AIC as a relevant cortical substrate linking nociceptive and affective processes and support CBD as a promising psychopharmacological strategy for NP associated with emotional comorbidities.”

https://pubmed.ncbi.nlm.nih.gov/42390818

“In conclusion, this study demonstrates that CBD microinjection into the AIC attenuates mechanical and cold allodynia while also reducing anxiety- and depression-like behaviors in an experimental model of NP.”

“Overall, these findings highlight the AIC as a potential neural substrate involved in the interaction between chronic pain and its emotional comorbidities and identify CBD as a promising psychopharmacological approach for NP conditions associated with affective dysfunction.”

https://link.springer.com/article/10.1007/s00213-026-07116-6

UK Medical Cannabis Registry: A Clinical Outcomes Analysis for Autism Spectrum Disorder

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“Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with distressed behaviors and psychological challenges. This study aims to evaluate the change in health-related quality of life (HRQoL), anxiety, and sleep quality in autistic individuals prescribed cannabis-based medicinal products (CBMPs).

Method: This observational case series analyzed data from the UK Medical Cannabis Registry on autistic adults treated with CBMPs. Demographic and clinical data were collected at baseline, with patient-reported outcome measures assessed up to 18 months. Primary outcomes included changes in anxiety (GAD-7), sleep quality (SQS), and HRQoL (EQ-5D-5L). Secondary outcomes included the incidence of adverse events. Statistical significance was indicated by p < 0.050.

Results: One-hundred and thirty individuals met the inclusion criteria. GAD-7 (p < 0.001) and SQS (p < 0.001) scores improved from baseline to 18 months. EQ-5D-5L index values showed improvement from baseline (0.43 ± 0.30) to 18 months (0.51 ± 0.32, p < 0.001), and PGIC scores increased from 1 month (5.43 ± 1.49) to 18 months (5.65 ± 1.32, p = 0.013). Twenty-five participants (19.23%) reported a total of 232 (178.46%) adverse events, with most being mild (n = 88; 67.69%) or moderate (n = 99; 76.15%).

Conclusion: Treatment with CBMPs was associated with improvements in HRQoL, anxiety, and sleep outcomes in autistic patients over an 18-month period. Given the absence of a control group, these findings represent associations rather than proven treatment effects. Further high-quality randomized controlled trials are needed to confirm the long-term efficacy and safety of CBMPs in ASD.”

https://pubmed.ncbi.nlm.nih.gov/42387975

“The endocannabinoid system (ECS) is a widespread neuromodulatory network that has been linked to the pathophysiology of ASD and is viewed as a potential target for drug development.”

“This observational study suggests that CBMP initiation in autistic adults is associated with improvements in HRQoL, anxiety, and sleep quality over 18 months. There was a favorable safety profile, with 80.77% of patients not reporting any adverse events.”

https://onlinelibrary.wiley.com/doi/10.1002/npr2.70146

Cannabis Oil Prevents Early Hepatic Fibrosis, Inflammation, and Endothelial Dysfunction in a Sucrose-Rich Diet-Induced MASLD Model: Role of Cannabinoid Receptors

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“Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern globally, often associated with excessive sugar intake and metabolic dysregulation. In this study, we explored early hepatic alterations induced by a short-term sucrose-rich diet (SRD) and evaluated the preventive effects of a full-spectrum cannabis oil (CO) with a CBD:THC ratio of 2:1.

Methods: Male Wistar rats were assigned to three groups: reference diet, SRD, and SRD plus CO (SRD + CO). CO was administered daily to the SRD + CO group from the onset of SRD exposure and throughout the 3-week experimental period. Liver fibrosis was assessed through hydroxyproline content, total collagen, TGF-β, and CB1R expression. Endothelial dysfunction was evaluated by measuring nitric oxide (NO) levels, endothelial nitric oxide synthase, myeloperoxidase, and VCAM-1 expression. Inflammatory responses were analyzed through hepatic expression of IL-10, TNF-α, PAI-1, MCP-1, F4/80, and CB2R. Transmission electron microscopy was performed on liver tissue to evaluate ultrastructural alterations.

Results: SRD induced significant hepatic fibrosis, endothelial dysfunction, and inflammation. Ultrastructural analysis revealed nuclear alterations, including chromatin condensation, reduced mitochondrial number, intracellular lipid accumulation, increased glycogen deposits, and stromal changes characterized by perisinusoidal and periportal fibrosis with inflammatory cell infiltration. CO administration attenuated these pathological features and was accompanied by modulation of cannabinoid receptor expression.

Conclusion: These findings highlight the preventive effects of CBD- and THC-containing CO against early liver alterations associated with MASLD.”

https://pubmed.ncbi.nlm.nih.gov/42367574

“Phytocannabinoids, such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), interact with the ECS and various other signaling pathways, providing antioxidant, anti-inflammatory, and antifibrotic properties. Full-spectrum cannabis extracts, which combine phytocannabinoids like CBD and THC, have emerged as therapeutic candidates in preclinical studies for the treatment of liver disorders associated with metabolic dysfunction. Previous studies conducted by our group have demonstrated hepatoprotective and antioxidant effects following the administration of full-spectrum COs in rats fed an SRD for 3 weeks.”

“The present study was designed to evaluate the preventive effects of daily CO administration during the early stages of SRD-induced MASLD.”

“Daily CO administration prevented these alterations and the SRD-induced increase in cannabinoid receptor protein levels.”

“These findings position ECS modulation – particularly through phytocannabinoid combinations – as a promising multi-target strategy capable of mitigating the earliest pathogenesis processes underlying MASLD.”

https://karger.com/mca/article/9/1/163/950066/Cannabis-Oil-Prevents-Early-Hepatic-Fibrosis

Cannabidiol alleviates traumatic brain injury-induced neuronal damage and cognitive deficits by inhibiting ferroptosis via the TRPV1/MCU/PI3K/Akt pathway

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“Background: Traumatic brain injury (TBI) is a common surgical traumatic condition that poses a significant threat to human health and working capacity. However, effective treatments to improve its prognosis remain limited. Cannabidiol (CBD), a naturally occurring compound extracted from the cannabis plant, exhibits multiple pharmacological effects through diverse molecular targets. To date, the role and underlying molecular mechanisms of CBD in the context of TBI have not been fully elucidated. In this study, we investigated the specific effects of CBD following TBI and explored its underlying mechanisms.

Methods: An in vitro ferroptosis model was established using HT-22 cells, and an in vivo TBI model was established in mice. Techniques such as Western blotting, immunofluorescence staining, and behavioral analysis were employed to evaluate the effects of CBD on ferroptosis, pathological changes, and neurological function after TBI, as well as to explore the associated molecular mechanisms.

Results: CBD significantly alleviated ferroptosis, neuronal injury, and cognitive dysfunction following TBI in vitro and in vivo. Further investigation revealed that CBD mitigated mitochondrial dysfunction by reducing Ca2⁺ overload via the TRPV1/MCU signaling pathway. Moreover, utilizing methodologies such as recombinant adeno-associated virus (rAAV) injection and transcriptome analysis, mitochondrial calcium uniporter (MCU) was identified as a core regulator of ferroptosis in neurons following TBI. Neuronal MCU knockdown attenuated the progression of ferroptosis and improved neurological outcomes after TBI. Finally, integrated findings confirmed that CBD inhibit ferroptosis after TBI through the TRPV1/MCU/PI3K/Akt signaling pathway.

Conclusions: CBD inhibits ferroptosis, at least in part, via the TRPV1/MCU/PI3K/Akt signaling pathway, thereby alleviating TBI-induced neuronal damage and cognitive deficits. In addition, these findings indicate that CBD exhibits a potent anti-ferroptotic effect and may serve as a promising therapeutic agent for TBI.”

https://pubmed.ncbi.nlm.nih.gov/42365227

https://link.springer.com/article/10.1186/s11658-026-00983-z

Modulation of Respiratory Diseases by the Endocannabinoid System: A Therapeutic Perspective

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“Respiratory system diseases represent a major global health burden, characterized by high prevalence and significant morbidity and mortality.

The respiratory tract’s direct and continuous exposure to the external environment makes it particularly vulnerable to pathogens, pollutants and other injurious agents. This exposure often triggers excessive inflammatory responses and compromises the integrity of the air-blood barrier, leading to impaired gas exchange, hypoxia and respiratory failure. Therefore, modulating pulmonary inflammation and enhancing barrier function are critical therapeutic objectives.

The endocannabinoid system, a ubiquitous signalling network comprising cannabinoid receptors, endogenous ligands and metabolic enzymes, has emerged as a crucial modulator of these processes.

This review summarizes the role of the ECS in major respiratory diseases, including asthma, pulmonary fibrosis, respiratory syncytial virus infection and acute lung injury.

The evidence highlights the therapeutic potential of targeting the ECS through strategies such as receptor-specific ligands and inhibitors of endocannabinoid-degrading enzymes. However, the context-dependent nature of ECS modulation necessitates precise intervention.

Future efforts should focus on developing selective therapeutics and validating their efficacy in clinical settings, positioning the ECS as a sophisticated target for innovative respiratory disease management.”

“Lung diseases such as asthma, fibrosis and infections are major health problems worldwide. The lungs are constantly exposed to the outside air, making them vulnerable to harmful substances that cause inflammation and damage. This review explores how a natural signalling system in our body—called the endocannabinoid system—helps control lung inflammation and repair. We summarize recent findings on how this system affects different lung diseases and discuss new treatment strategies that target it. While promising, these approaches need to be precisely targeted because the system works differently depending on the specific disease. Understanding this system could lead to better treatments for patients with lung diseases.”

https://pubmed.ncbi.nlm.nih.gov/42363690

“The endocannabinoid system plays a pivotal role in modulating key pathological processes in respiratory diseases, including inflammation, fibrosis, airway hyperresponsiveness and barrier dysfunction. CB2R activation generally exerts anti-inflammatory and anti-fibrotic effects, while CB1R influences airway tone and tissue remodelling. Enhancing endocannabinoid levels through inhibition of metabolic enzymes such as FAAH and MAGL also shows therapeutic potential in attenuating lung injury. However, the context-dependent and pleiotropic nature of ECS signalling necessitates precise, disease-specific targeting.

Future efforts should focus on developing receptor-selective agents and advancing translational studies to harness the ECS as a viable therapeutic strategy in respiratory medicine.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.70267

“The potential of cannabinoids and inhibitors of endocannabinoid degradation in respiratory diseases”

https://pubmed.ncbi.nlm.nih.gov/34648805


Endocannabinoid signalling in the regulation of hypothalamic-pituitary neuroendocrine circuits: A review

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“The endocannabinoid system (ECS), comprising cannabinoid receptors, endogenous lipid ligands, and enzymes that regulate their synthesis and degradation, has emerged as an important modulator of neuroendocrine regulation.

This review summarises current evidence on the role of endocannabinoid signalling in hypothalamic-pituitary neuroendocrine circuits, with particular focus on the hypothalamic-pituitary-adrenocortical, gonadal, thyroid, and somatotropic axes, as well as prolactin and posterior pituitary hormones regulation.

Available data indicate that endocannabinoid signalling predominantly influences neuroendocrine function by modulating synaptic transmission within hypothalamic circuits. Acting mainly as retrograde messengers at presynaptic CB1 receptors, endocannabinoids regulate excitatory and inhibitory inputs to neurosecretory neurons and thus shape endocrine output in a context-dependent manner.

Among the systems discussed, the hypothalamic-pituitary-adrenocortical axis is the best characterised, with relatively well-defined links between glucocorticoid feedback and rapid endocannabinoid-mediated suppression of synaptic input to corticotropin-releasing hormone neurons.

In other neuroendocrine systems, evidence supports a predominantly modulatory, often inhibitory, role for endocannabinoid signalling, although the underlying cellular processes remain less well-defined and are largely based on preclinical studies. Interactions with glucocorticoids, gonadal steroids and neuropeptidergic pathways further underscore the integrative nature of ECS signalling.

Overall, the ECS should be viewed not as a primary endocrine driver, but as a dynamic regulatory network that fine-tunes the translation of neural activity into hormonal responses.”

https://pubmed.ncbi.nlm.nih.gov/42365630

https://reference-global.com/article/10.2478/enr-2026-0011


Cannabidiol as an adjunct in refractory paroxysmal sympathetic hyperactivity following severe traumatic brain injury: a case report

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“Background: Paroxysmal Sympathetic Hyperactivity (PSH) is a well-recognized complication following severe traumatic brain injury (TBI), with an incidence of 5-33% in the acute phase, characterized by episodic autonomic and motor hyperactivity. Management is often challenging, and a subset of patients develop refractory PSH despite optimized first- and second-line therapies. Cannabidiol (CBD) possesses neuroregulatory and autonomic-modulating properties demonstrated in preclinical TBI studies and epilepsy trials including Epidiolex studies, but its role in PSH has not been previously described.

Case presentation: We report the case of a 44-year-old South Indian gentleman with severe TBI following a road traffic accident (GCS 5: E1V1M3) with CT brain showing bilateral frontotemporo-parietal acute subdural hematoma with mass effect. He underwent emergency bilateral decompressive craniectomy and required mechanical ventilation with tracheostomy. Three weeks post-injury, he developed recurrent PSH episodes (4-6 episodes per day) characterized by severe tachycardia (heart rate 140-180 bpm), hypertension (systolic blood pressure > 180 mmHg), hyperthermia (up to 40 °C), diaphoresis, and dystonic posturing. The diagnosis of PSH was established using the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM), with a total score of 28 (Clinical Feature Scale: 18, Diagnosis Likelihood Tool: 10), indicating probable PSH. Infective, metabolic, epileptic, and structural causes were excluded. Despite treatment with multiple conventional agents at maximum tolerated doses-including bromocriptine (titrated from 1.25 mg twice daily to 40 mg/day), baclofen (10 mg/day), gabapentin (titrated from 150 mg/day to 300 mg/day), propranolol (15 mg three times daily), clonidine (0.2 mg/day), dexmedetomidine infusion (72-h infusion), and fentanyl (infusion followed by patches)-the autonomic storms persisted, fulfilling criteria for refractory PSH.

Cannabidiol oil (100 mg/mL) was therefore initiated as adjunctive therapy at 100 mg twice daily (approximately 3 mg/kg/day) and titrated to a 100-150-100 mg/day regimen over one week via nasogastric tube. Within the first week, there was a marked reduction in episode frequency (from 4 to 6 per day to less than 1 per 48 h) and severity, with PSH-AM scores decreasing from 28 (CFS: 18, DLT: 10) to 16 (CFS: 6, DLT: 10), and opioid and sedative infusions were successfully withdrawn. By the second week, complete resolution of PSH episodes was achieved with a PSH-AM score of 4. No adverse effects were observed, including no hepatic dysfunction, excessive sedation, or hemodynamic instability.

Conclusions: This case highlights a potential adjunctive role for cannabidiol in refractory PSH following severe TBI. While causality cannot be inferred from a single observation, the sustained clinical improvement after failure of conventional therapies warrants further prospective investigation.”

https://pubmed.ncbi.nlm.nih.gov/42366387

https://link.springer.com/article/10.1186/s13256-026-06284-5