Use of Purified Cannabidiol in Treatment-Resistant Pediatric Epilepsy: Beyond Lennox-Gastaut Syndrome, Dravet Syndrome, and Tuberous Sclerosis Complex

Purified cannabidiol may help a much broader range of children with treatment-resistant epilepsy than the three syndromes for which it is currently FDA-approved. In this real-world study of 144 pediatric patients, 63 had epilepsy diagnoses outside Lennox–Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex.

The response rate was nearly identical between the groups. At least a 50% reduction in seizure frequency was documented in 65% of children with an FDA-labeled diagnosis and 63% of those with other forms of epilepsy. The median age when CBD was started was 10 years, and patients were already taking a median of three other antiseizure medications.

The authors concluded that purified CBD was effective across a broad range of treatment-resistant pediatric epilepsies and was generally well tolerated as an add-on antiseizure medication. They specifically state that CBD may be considered in pharmacoresistant pediatric epilepsy beyond its currently labeled indications.

“Background: The pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex) is approved by the the US Food and Drug Administration for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis in patients one year of age and older. Among the large volume of drug-resistant cases treated at pediatric Level 4 Epilepsy Centers, many patients fall outside of these categories but are still prescribed CBD for off label use. This study sought to characterize the real-world experience with CBD of a large single pediatric comprehensive epilepsy center and to compare response to CBD within and outside of its FDA-approved indications.

Methods: A retrospective chart review was performed of patients with a prescription for CBD at our institution between January 2020 and January 2022, excluding patients who were previously included in our center’s 2019 analysis. Patients were not included in the analysis if initially prescribed CBD elsewhere, follow-up was outside our institution, medication was not started, patient expired during the study period, or diagnostic data was not available. Between-group differences were assessed via Wilcoxon rank-sum and Fisher exact tests, as appropriate.

Results: Of 223 patients with a CBD prescription during the study period, 144 patients had sufficient data available for review. Of these patients, 81 (56%) carried diagnoses of Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis, and 63 (44%) carried other diagnoses outside of FDA-labeled indications. Median (interquartile range) age at initiation was 10.0 years (5.0, 13.0), and median (interquartile range) number of concurrent anti-seizure medications was 3.0 (2.0, 3.0). There was no significant difference in the proportion of patients treated concurrently with vagus nerve stimulation or ketogenic diet between the two groups. The FDA-labeled (63%) group had a significantly higher proportion of patients with tonic seizures compared to the non-FDA labeled (29%) group (P < 0.001), otherwise there were no significant differences in baseline seizure types. Overall, 53 patients (65%) in the FDA-labeled group and 40 (63%) of the non-FDA labeled group had a documented responder rate at least 50% on CBD (P = 0.9). The most common side effects reported were nausea/diarrhea/gastrointestinal upset (19%), agitation (7.6%), insomnia (4.9%), weight loss (6.3%), and secretions/drooling (2.8%, seen only in patients on concurrent clobazam).

Conclusions: Among our cohort of treatment-resistant pediatric epilepsy, purified CBD was efficacious in a broad range of pediatric epilepsies and was well tolerated as an adjunctive anti-seizure medication. This medication may be considered in pharmacoresistant pediatric epilepsies in conditions beyond its FDA-labeled indications.”

https://pubmed.ncbi.nlm.nih.gov/42753320

https://www.pedneur.com/article/S0887-8994(26)00274-2/abstract

Exploring the potential benefits of combining cannabidiol and beta-caryophyllene for neuropathic and inflammatory pain: A systematic review

A new systematic review found that combining cannabidiol (CBD) with beta-caryophyllene (BCP) consistently reduced neuropathic and inflammatory pain in preclinical studies. The review searched research published from 2009 through 2026 and identified five studies that met its inclusion criteria, all using rodent pain models.

Across those studies, the CBD–BCP combination reduced both neuropathic and inflammatory pain, with the authors describing evidence of a possible synergistic analgesic effect. Importantly, the reported pain relief was not accompanied by the central adverse effects associated with cannabinoid receptor 1 (CB1) activation.

The authors concluded that CBD and beta-caryophyllene may work together synergistically in chronic pain and said the findings provide a rationale for future preclinical and clinical studies. Because the evidence so far is entirely preclinical, the next step is determining whether the same combination can produce meaningful pain relief in people.

“Purpose: In this review, we examined the analgesic effect of the combination of cannabidiol (CBD) and beta-caryophyllene (BCP) in different pain conditions.

Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature searches were performed across major academic databases (Google Scholar, Web of Science, and PubMed) from 2009 to 2026 to identify studies investigating the analgesic effect of the combination of CBD and BCP.

Results: The search identified 31 records. Ten reports were screened and assessed for eligibility, and five studies met the inclusion and exclusion criteria. Findings consistently demonstrate that the combination of CBD and BCP reduces neuropathic and inflammatory pain in rodent models. This effect does not result in adverse outcomes associated with cannabinoid receptor 1 (CB1). This review discusses potential mechanisms by which this combination produces synergistic analgesic effects.

Conclusion: The literature discussed in this review suggests that the combination of CBD and BCP can work in synergy in chronic pain without cannabinoid receptor 1 central side effects. These preclinical findings provide the rationale for future preclinical and clinical studies.”

https://pubmed.ncbi.nlm.nih.gov/42753475

“In summary, these data suggest that combining CBD and BCP may be especially effective in reducing neuropathic pain caused by spinal cord injury. Additionally, this combination resulted in minimal cannabinoid-like side effects.”

https://www.sciencedirect.com/science/article/pii/S0944711326010287?via%3Dihub

Effect of solvent polarity on phenolic antioxidant extraction from Cannabis sativa L. leaves and inflorescences: mixture design optimization and HPLC-DAD/ESI-MS2 profiling

A new 2026 study shows that how cannabis is extracted can dramatically change which beneficial compounds are recovered. Researchers tested water, ethanol and acetone mixtures on Cannabis sativa leaves and inflorescences and found that solvent composition significantly affected total phenolics, cannabinoids and antioxidant activity.

Inflorescences produced their highest total phenolic content — 16.05 mg GAE/g dry weight — with an acetone-rich mixture, while leaves reached 13.65 mg GAE/g with one-third ethanol and two-thirds acetone. Chemical profiling identified 32 compounds, including phenolic acids, flavonoids, hydroxycinnamic acid amides, lignanamides and cannabinoid derivatives.

The extracts also showed notable antioxidant activity across DPPH, ABTS, FRAP, CUPRAC and TAC assays. The authors concluded that cannabis leaves and flowers may be valuable targeted sources of antioxidant phytochemicals for pharmaceutical, nutraceutical and cosmetic applications.

“Cannabis (Cannabis sativa L.) is a source of bioactive compounds with promising applications in the nutraceutical, pharmaceutical, and cosmetic fields.

Applying a mixture design approach with three solvents (water, acetone and ethanol), this study investigated how solvent composition modulates the recovery of phenolic compounds from cannabis inflorescences and leaves. Extracts were assessed for total phenolic content (TPC) and antioxidant activities using DPPH, ABTS, FRAP, CUPRAC, and TAC assays, and their chemical profiles were characterized by HPLC-DAD/ESI-MS2.

Solvent composition significantly affected extraction efficiency across plant organs. For inflorescences, the highest TPC value (16.05 mg GAE per g dry weight) was obtained with an acetone-enriched mixture (1/6 water-1/6 ethanol-2/3 acetone), whereas leaves reached their maximum (13.65 mg GAE per g DW) with 1/3 ethanol-2/3 acetone.

Multi-response optimization identified 1/3 water-1/3 ethanol-1/3 acetone for inflorescences and 50% water-30% ethanol-20% acetone for leaves as the optimal solvent mixtures.

HPLC-DAD/ESI-MS2 analysis identified 32 compounds belonging to several classes, including phenolic acids, flavonoids, hydroxycinnamic acid amides, lignanamides, and cannabinoid derivatives. These classes showed diverse content depending on the solvent and plant matrix. The acetone rich mixture produced the highest total cannabinoids (10.56 and 8.45 mg CBN equivalents per g dry weight) for inflorescences and leaves, respectively.

These results reveal clear organ and solvent-dependent selectivity in Moroccan Cannabis. These differences were reflected in the antioxidant activities, with extracts showing notable reducing and radical-scavenging capacities across DPPH, ABTS, FRAP, CUPRAC, and TAC assays.

These findings support the targeted valorization of cannabis leaves and inflorescences as sources of antioxidant phytochemicals for pharmaceutical and cosmetic applications.”

https://pubmed.ncbi.nlm.nih.gov/42751042

“The chemical diversity of Cannabis sativa metabolites has stimulated extensive research into their extraction and characterization. In this study, water, ethanol, and acetone were combined to enhance the extraction of phenolic compounds and antioxidants from Cannabis sativa L. leaves and inflorescences.

Multi-response optimization showed that each plant matrix required a specific optimal solvent mixture, confirming matrix-dependent extraction behavior: 1/3 water–1/3 acetone–1/3 ethanol for inflorescences and 50% water–30% ethanol–20% acetone for leaves. HPLC-DAD/ESI-MS2 enabled the tentative identification of several compound classes, including cannabinoids, hydroxycinnamic acid amides, flavonoids, and lignanamides. Inflorescences were characterized by higher total cannabinoid contents, whereas leaves contained higher levels of hydroxycinnamic acid amides. These differences highlight both the importance of solvent selection and the distinct chemical composition of Cannabis sativa L. organs.

Overall, these results support the potential valorization of the optimized Cannabis sativa leaf and inflorescence extracts as sources of antioxidant and bioactive compounds for prospective applications in natural cosmetic formulations, such as antioxidant creams, serums or other topical skincare products, as well as in nutraceutical formulations, including functional supplements enriched with plant-derived antioxidants. However, additional studies on formulation stability, bioavailability, efficacy, and safety are required before practical application.”

https://pubs.rsc.org/ra/article/doi/10.1039/d6ra05874d/1356587/Effect-of-solvent-polarity-on-phenolic-antioxidant

Standardized Curcuma longa-Cannabis sativa extract derived from a traditional Thai formulation for psoriasis: anti-inflammatory activity, keratinocyte modulation, and skin-targeted delivery

A new study tested a standardized combination of Curcuma longa (turmeric) and Cannabis sativa derived from a traditional Thai topical formulation for psoriasis. The combined extract contained curcuminoids, ar-turmerone and cannabidiol, including 35.47 mg/g CBD, and was evaluated for anti-inflammatory activity, effects on psoriasis-related keratinocytes and its ability to remain concentrated in the skin.

At 12.5 µg/mL, the combined extract reduced nitric oxide production by 48.97% and PGE₂ production by 91.15%. It also altered psoriasis-associated gene expression in TNF-α/IL-17A-stimulated keratinocytes, showing activity against several biological processes involved in psoriasis.

The skin-delivery experiments found strong deposition of the extract’s markers in the skin, with none detected in the receptor compartment during the 24-hour test. The authors concluded that the standardized turmeric–cannabis combination showed anti-inflammatory, psoriasis-relevant and skin-targeted activity supporting further development as a localized phytotherapeutic approach for psoriasis.

“Ethnopharmacological relevance: Curcuma longa rhizomes and Cannabis sativa leaves are traditionally combined in Thai topical remedies using cottonseed oil. However, the pharmacological basis and dermal delivery of this combination remain unclear.

Aim of the study: This study evaluated a standardized Thai CL-CS combined extract (CLCS) by integrating phytochemical characterization, psoriasis-relevant biological activities, and ex vivo skin deposition and permeation, with comparison to the single extracts.

Materials and methods: CLCS was standardized by validated HPLC using curcuminoids, ar-turmerone, and cannabidiol as markers. Anti-inflammatory activity was evaluated in RAW264.7 macrophages, while psoriasis-relevant activity was assessed in TNF-α/IL-17A-stimulated HaCaT keratinocytes. Skin deposition and permeation were evaluated using porcine ear skin and Franz diffusion cells.

Results: CLCS contained bisdemethoxycurcumin (18.79 ± 1.54 mg/g), demethoxycurcumin (12.89 ± 1.02 mg/g), curcumin (22.12 ± 1.62 mg/g), ar-turmerone (75.35 ± 3.94 mg/g), and cannabidiol (35.47 ± 2.39 mg/g). IC50 values were 41.22 ± 1.70 and 22.91 ± 0.51 μg/mL in HaCaT and RAW264.7 cells, respectively. At 12.5 μg/mL, CLCS inhibited NO and PGE2 production by 48.97 ± 0.88% and 91.15 ± 3.66%, respectively, and modulated psoriasis-associated genes. Cottonseed oil containing 20% DG achieved the highest skin deposition of BCM, DCM, and CM, with no detectable markers in the receptor compartment over 24 h.

Conclusions: Standardized CLCS exhibited anti-inflammatory and psoriasis-relevant activities and preferential skin deposition, supporting its potential as a localized phytotherapeutic approach for psoriasis.”

https://pubmed.ncbi.nlm.nih.gov/42772617

“The present study provides an integrated chemical, biological, and skin-targeted delivery evaluation of a standardized CLCS co-extract derived from a traditional Thai topical formulation. The extract was successfully standardized by its characteristic bioactive constituents derived from both botanical components. CLCS demonstrated anti-inflammatory and psoriasis-relevant biological activities”

https://www.sciencedirect.com/science/article/abs/pii/S0378874126012833?via%3Dihub

Computational and Comparative In Vitro Evaluation of GC-MS Profiled Cannabis sativa Inflorescence Extracts’ Metabolites on Selected Diabetes Therapeutic Targets

A new 2026 study found that Cannabis sativa flower extracts showed activity against several biological targets involved in diabetes. Researchers tested the extracts for effects on carbohydrate-digesting enzymes, glucose uptake and oxidative stress, then used computational modeling to examine how 36 cannabis metabolites interacted with diabetes-related proteins.

The hexane extract showed the strongest overall activity, including inhibition of α-amylase and α-glucosidase and the greatest increase in glucose uptake in the yeast model. Glucose uptake with the hexane extract rose from 25% at 62.5 µg/mL to 54% at 500 µg/mL.

The docking analysis identified several cannabinoids — including Δ9-THC, 8-hydroxy-Δ9-THC, cannabivarin and tetrahydrocannabinol-7-oic acid — as promising candidates for further study against diabetes-related targets such as DPP-4, SGLT-2 and PTP1B. The authors concluded that cannabis inflorescences may be a promising source of compounds for future antidiabetic drug research.

“Cannabis sativa, a medicinal plant rich in cannabinoids, terpenoids, and flavonoids, has been shown to have various pharmacological activities.

This study investigated the antidiabetic potential of C. sativa inflorescence extracts using in vitro and computational models.

Dried C. sativa inflorescences were extracted sequentially with hexane, dichloromethane, and methanol, before their metabolites were identified by GC-MS. The extracts were tested for α-amylase and α-glucosidase inhibition, glucose uptake activity, and antioxidant effects using DPPH and nitric oxide (NO) inhibition assays. Thirty-six metabolites were further docked against diabetes-related proteins.

Among the extracts, the hexane extract showed the strongest bioactivity with notable α-amylase inhibition (IC50: 727 µg/mL), DPPH free radical scavenging (IC50: 478.62 µg/mL), and nitric oxide inhibition activity (IC50: 356.51 µg/mL). Docking analyses revealed strong binding affinities for 8-hydroxy-delta-9-THC, cannabivarin, and 9-tetrahydrocannabinol with DPP-4, PTP1B, and other target proteins.

These findings highlight the potential of C. sativa inflorescences as a source of antidiabetic agents, warranting further in vivo and clinical validation.”

https://pubmed.ncbi.nlm.nih.gov/42763912

“This study provides preliminary evidence that C. sativa inflorescence extracts contain phytoconstituents with antioxidant, enzyme-inhibitory, and potential antidiabetic activities under the experimental conditions investigated. Among the extracts, the hexane extract exhibited the strongest enzyme inhibition and capacity to interact with free radicals.

In addition, compounds including Δ9-tetrahydrocannabinol, 8-hydroxy-Δ9-THC, cannabivarin, and tetrahydrocannabinol-7-oic acid exhibited favorable binding affinities toward diabetes-related protein targets, identifying them as promising candidates for further investigation.”

https://onlinelibrary.wiley.com/doi/10.1002/cbdv.71684

Dose Response Relationship of Medical Cannabis and Symptom Control in Patients With Pancreatic Cancer: An Analysis of the CANPAN Trial

A new analysis of the CANPAN trial found a clear dose-response relationship between THC and symptom improvement in patients with pancreatic cancer. The trial enrolled 32 cannabis-naïve patients with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma, and 23 used medical cannabis during their assigned eight-week treatment period.

Higher average daily THC doses were significantly associated with greater improvements in anxiety and insomnia. Patients receiving at least 10 mg of THC per day improved in an average of four symptoms, compared with 2.1 symptoms among patients receiving less than 10 mg per day.

The authors say these findings provide important dose-response information for future pancreatic-cancer trials, particularly for psychological symptoms and multi-symptom control. The results add to evidence from the CANPAN trial that personalized medical cannabis may have a role in managing symptoms experienced by people undergoing treatment for pancreatic cancer.

“Background: In a pilot waitlist-control randomized trial, a personalized medical cannabis intervention improved certain symptoms among patients with pancreatic cancer over 8 weeks. Longer-term and dose-response data can guide future trial design.

Methods: CANPAN enrolled 32 cannabis-naïve patients with newly diagnosed locally advanced/metastatic pancreatic adenocarcinoma (NCT06605430). Patients were randomized to early (0-8 weeks) or delayed (9-16 weeks) cannabis intervention. Primary efficacy results over the first 8 weeks were previously reported. We investigated cannabis use and patient-reported outcome (PRO) completion over 9-16 weeks, and the relationship between tetrahydrocannabinol (THC) dose and symptom efficacy.

Results: Among 32 participants, 23 (72%) used cannabis during their assigned 8-week period (12/16 in early arm and 11/16 in delayed arm). Of these, 16 (50%) had both pre-cannabis and 8-week post-cannabis initiation PRO data available. At the end of the 16-week study period, PRO data were available for 16 (50%) participants (9/16 early arm, 7/16 delayed arm). Median daily THC dose 4 weeks after starting cannabis was similar in early vs delayed arms (10 mg vs 9.3 mg). A higher average daily THC dose was associated with improvements in anxiety (r 0.52, p = 0.038) and insomnia (r 0.53, p = 0.033). A ≥ 10 mg daily THC dose (vs < 10 mg) was associated with mean improvement in 4 vs 2.1 symptoms.

Conclusions: The 50% complete data availability at 16 weeks, dose-response relationship with psychological symptoms, and threshold dose for multi-symptom efficacy will guide future trials. Similar cannabis use patterns across arms raise confidence in the waitlist-control design.”

https://pubmed.ncbi.nlm.nih.gov/42767994

https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyag374/8826188

Delta-9-tetrahydrocannabinol alleviates inflammation by modulating immune responses in LPS-induced murine inflammation model

Delta-9-THC reduced inflammatory immune signaling across human immune cells and a mouse model of systemic inflammation. In LPS-stimulated cells, THC markedly suppressed type I interferon-related genes and pro-inflammatory cytokines including IL-1β and TNF-α, while also reducing immune-cell activation markers.

The effects extended beyond isolated cells. In mice exposed to systemic inflammation, THC reduced activation of splenic myeloid cells and T cells. Brain analysis also showed reduced neuroinflammatory signaling, including lower expression of inflammatory mediators, while pathways associated with neurogenesis, synaptic plasticity and neuronal function were enriched.

Importantly, the researchers describe THC’s effects as modulation rather than indiscriminate immune suppression, concluding that THC appears to dampen excessive inflammatory signaling while influencing cellular stress-adaptation pathways. They say these findings support further investigation of cannabinoid signaling in chronic inflammatory, neuroimmune and neurodegenerative disorders.

“Introduction: Δ9-Tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has been reported to modulate immune responses; however, its effects on complex innate immune signaling pathways and inflammation remain incompletely understood. Here, we investigated the immunomodulatory effects of THC on lipopolysaccharide (LPS)-induced inflammation across cellular and in vivo models.

Methods: We integrated transcriptomic, cellular, and in vivo approaches to characterize the effects of THC on innate immune activation. Human THP-1 monocytic cells were treated with THC in the presence or absence of LPS, followed by transcriptomic and gene expression analyses to evaluate inflammatory, type I interferon, unfolded protein response (UPR), and autophagy pathways. Findings were validated in primary human monocytes by assessing immune activation markers. The effects of chronic THC exposure were further evaluated in a murine model of systemic inflammation by examining splenic myeloid and T-cell activation. RNA sequencing of brain tissue was performed to assess the effects of THC on neuroinflammatory and neuronal pathways.

Results: THC induced a stress-adaptive transcriptional program in THP-1 cells, characterized by upregulation of genes associated with the UPR and autophagy pathways. In contrast, THC markedly suppressed LPS-induced type I interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including IL-1β and TNF-α. In primary human monocytes, THC significantly reduced the expression of activation markers CD80, CD83, and CD209. Consistent with these findings, chronic THC exposure attenuated the activation of splenic myeloid and T cells in mice subjected to systemic inflammation. Brain transcriptomic analysis further demonstrated reduced expression of neuroinflammatory pathways following THC exposure, accompanied by enrichment of pathways associated with neurogenesis and synaptic plasticity.

Discussion: Our findings demonstrate that THC exerts broad immunomodulatory effects characterized by suppression of inflammatory and type I interferon responses while promoting cellular stress-adaptation pathways. These effects were observed across human monocytic cells, primary monocytes, and peripheral immune populations in vivo, and were accompanied by reduced neuroinflammatory signaling and increased neuronal plasticity-associated pathways in the brain. Together, these findings provide mechanistic insight into the immunomodulatory actions of THC and support further investigation of cannabinoid signaling as a potential regulator of chronic inflammatory and neuroimmune disorders.”

https://pubmed.ncbi.nlm.nih.gov/42818626

“Chronic THC exposure reduces LPS-induced immune activation in vivo.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1856131/full

Need this THC study explained? thcXplained.com

Effectiveness and safety of cannabidiol in adult patients with epilepsy: A multicenter, retrospective study

A new multicenter study found that cannabidiol was associated with substantial seizure reductions in adults living with severe, drug-resistant forms of epilepsy. The study followed 37 adults with Dravet syndrome, Lennox–Gastaut syndrome, or tuberous sclerosis complex who received CBD for at least 12 months.

After six months, 48.6% of patients had at least a 50% reduction in seizure frequency; after 12 months, 45.9% still met that threshold. Caregivers also reported improvements in alertness, behavior, interaction, or daily functioning in 29.7% of patients, while the median number of other antiseizure medications fell from four to three.

The authors concluded that CBD was associated with “clinically meaningful seizure reduction and acceptable tolerability” in this real-world adult population. Adverse events occurred in 64.9% of patients but were mostly mild, and 81.1% remained on CBD at 12 months.

“Objective: Cannabidiol (CBD) has demonstrated promising effectiveness and tolerability as adjunctive treatment in patients with severe childhood epilepsies. This study investigated the effectiveness and tolerability of CBD in adults with a history of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC).

Methods: This was a multicenter, retrospective, observational study in adults with diagnosis of DS, LGS or TSC who received at least 12 months of CBD treatment. Medical records were reviewed and baseline characteristics, treatment retention, seizure frequency, cognitive behavioral improvements, concomitant ASM usage, and adverse events were assessed.

Results: Thirty-seven patients (median age 25 years; 67.5% male) with diagnosis of DS, LGS or TSC received CBD for at least 12 months. The CBD median maintenance dose was 10.45 mg/kg/day (IQR 7.455 – 13.975) (median maximum dose 11 mg/kg/day); median follow-up time was 28 months (IQR 22.75-58.25). Seizure frequency was reduced by ≥50% in 48.6% of patients at 6 months and 45.9% at 12 months. No statistically significant differences in median maintenance dose were observed across seizure reduction categories. During CBD treatment, caregivers reported subjective improvements in cognition in 29.7% of patients. Treatment with CBD was significantly associated with a reduction in the median number of concomitant ASMs at the end of follow-up (4 [3, 4]) vs. 3 [3, 4] (p = 0.022). AEs occurred in 64.9% of patients and were mostly mild; 16.2% had AEs leading to treatment discontinuation.

Significance: We present a series of adult patients treated with CBD according to label. The results are similar to those described in children. CBD treatment was associated with clinically meaningful seizure reduction and acceptable tolerability in this real-world cohort of adults with drug-resistant developmental and epileptic encephalopathies. These findings support the potential role of CBD in complex adult DEE populations while highlighting the need for prospective controlled studies to better define its independent treatment effect.

Plain language summary: This study looked at the long-term use of cannabidiol (CBD) in 37 adults with Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex. After 12 months, almost half of the patients had at least a 50% reduction in seizures. Some caregivers also reported improvements in cognition and behavior. Patients were able to reduce the number of other antiseizure medicines they were taking. Side effects were common but mostly mild, although a small number of patients stopped treatment because of them. Overall, CBD appeared effective and reasonably well tolerated, but further controlled studies are needed.”

https://pubmed.ncbi.nlm.nih.gov/42765195

“CBD has demonstrated promising effectiveness and tolerability in adult patients with a history of DS, LGS, or TSC. Treatment with CBD was associated with reductions in seizure frequency and in concomitant ASMs, which could improve treatment retention and reduce AEs. The findings support a growing body of evidence highlighting the efficacy of CBD across age groups and epilepsy etiologies in real-world clinical practice.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70331

Evaluating the impact of cannabinoid extracts on chronic pain and quality of life in endometriosis patients – a pilot study

Women with endometriosis and chronic pelvic pain experienced significant improvements after adding a balanced oral THC cannabis extract to their existing treatment. In this prospective pilot study, 27 women completed three months of treatment, with benefits appearing within the first month and continuing through the study period.

Pain intensity fell significantly, along with the number of pain days and the need for conventional pain medicines. Use of both NSAIDs and opioid analgesics decreased, while fatigue, anxiety, central sensitization and pain-related disability also improved.

Quality of life improved across every measured EHP-30 domain, including pain, emotional well-being, work impairment, self-image and sexual relationships. The authors concluded that balanced THC cannabinoid medicines appear to be a potentially effective adjunct treatment for chronic pelvic pain and related symptoms in women with endometriosis.

“Endometriosis is a chronic gynecological disorder characterized by persistent pain and impaired quality of life, with limited effective treatment options. Emerging evidence indicates that cannabinoids may provide analgesic and symptom-relieving effects in chronic pain conditions.

This prospective single-center cohort study investigated the effects of standardized oral cannabis extracts (cannabinoid-based medicinal products, CBMPs) on pain and quality of life in women with endometriosis.

Thirty premenopausal women aged 18-45 years with confirmed endometriosis and chronic pelvic pain were enrolled; 27 completed the 3-month treatment period. Participants received oral CBMPs containing a balanced THC: CBD ratio. Pain intensity, frequency of pain episodes, analgesic use, fatigue, anxiety, central sensitization, disability, and quality of life were assessed using validated questionnaires (VAS, EHP-30, PDI, CFS, GAD-7, CSI).

Significant improvements were observed after one month of treatment, with continued benefit over three months. Pain intensity decreased markedly (p = 0.0004), accompanied by reductions in the number of pain days and analgesic use, including both NSAIDs (e.g., ibuprofen, diclofenac) and opioid analgesics (e.g., tramadol, tilidin, oxycodone) (p < 0.001). Fatigue (p = 0.0013), anxiety (p < 0.0001), central sensitization (p < 0.0001), disability (p < 0.0001), and overall quality of life (EHP-30) improved significantly.

Treatment was well tolerated; side effects were predominantly mild (severity score 1 on a 0-3 scale) and transient, occurring mainly during the titration phase and declining thereafter. Although limited by its single-center design, lack of placebo control, and short follow-up, this study provides preliminary evidence that oral CBMPs may represent a safe and effective adjunct therapy for managing pain and related symptoms in women with endometriosis. Larger randomized controlled trials are warranted to confirm these findings and establish optimal dosing strategies.”

https://pubmed.ncbi.nlm.nih.gov/42771648

“In conclusion, oral CBMPs with balanced THC: CBD ratios seem to be a safe and potentially effective adjunct therapy for chronic pelvic pain and related symptoms in women with endometriosis. By targeting both nociceptive and neuropsychological aspects of the condition, CBMPs can supplement existing pharmacological and lifestyle strategies, providing a more comprehensive approach to symptom management. These findings establish a basis for future controlled studies to refine dosing, investigate mechanisms, and assess long-term outcomes in this complex patient group.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356768

Cannabinoids and therapeutic potential in neuropsychiatry

Cannabinoids are already used therapeutically in several areas of medicine, and a new review examines how that potential may extend into neuropsychiatry. The authors look beyond cannabis as a single drug, focusing instead on its individual cannabinoids and how different components may contribute to neurological and psychiatric effects.

The review highlights cannabidiol as the cannabinoid with the clearest established role in certain seizure disorders, while examining the broader literature on cannabinoids in neuropsychiatric illness. The authors argue that cannabis is more pharmacologically complicated than any one cannabinoid and that its therapeutic potential may depend on interactions among multiple plant components.

One of the review’s most important points is that combinations of cannabis components may ultimately prove more useful than isolated compounds alone. Rather than dismissing cannabis as having no medical utility in neuropsychiatry, the authors call for approaches that better investigate and use the therapeutic attributes of the plant.

“Cannabinoids have therapeutic utility in some specific areas of medicine, including as an anti-nausea adjunct for chemotherapy and as an anti-inflammatory agent, among others. However, as a therapeutic agent in neuropsychiatric conditions, the data is more limited. Cannabis itself is viewed as a recreational drug of abuse with no medical utility; however, the reality may be more complex when considering individual components of the plant.

Cannabinoid components may have some benefit as therapeutic agents in neuropsychiatry, with cannabidiol most often purported to be a therapeutic agent for some seizure disorders. However, recent studies suggest that the cannabis plant is proving to be broader and more complicated in how it delivers potential therapeutic effects. It may be that a combination of components is more effective than any one component.

This chapter reviews the medical usage of cannabinoids in neuropsychiatric illness, as reported in the literature, and proposes future approaches that may more effectively avail the attributes of this plant.”

https://pubmed.ncbi.nlm.nih.gov/42767714

“Cannabinoid treatments are carving a noteworthy niche in the pharmaceutical repertoire, offering new hope for conditions that have been historically difficult to manage, such as comorbid anxiety and epilepsy.”

https://www.sciencedirect.com/science/chapter/bookseries/abs/pii/S0074774226001303?via%3Dihub