Cannabinoids in Alzheimer’s disease: animal-human evidence and clinical pharmacology challenges

Posted on by

“Cannabinoids have emerged as potential modulators of pathological processes in Alzheimer’s disease (AD), including neuroinflammation, synaptic dysfunction, and protein aggregation. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main phytocannabinoids from Cannabis sativa, interact with the endocannabinoid system and may influence neuronal and glial signaling pathways relevant to AD pathology.

This mini review summarizes evidence from transgenic animal models and clinical studies evaluating CBD, THC, and their combination in AD.

Preclinical studies show that CBD and THC reduce β-amyloid accumulation, attenuate tau phosphorylation, and regulate neuroinflammatory responses, often associated with improvements in learning and memory. Cognitive outcomes appear to depend on cannabinoid composition, with CBD or THC administered individually showing more consistent effects, while combined CBD + THC effects appear dose- and ratio-dependent.

Clinical evidence in AD patients remains limited and primarily reports improvements in neuropsychiatric symptoms, such as reductions in agitation, nighttime activity, and behavioral disturbances, whereas cognitive improvements are modest. Cannabinoid-based treatments are generally well tolerated, with mild sedation, somnolence, or disorientation as the most reported adverse effects.

Overall, current data support the biological plausibility of cannabinoids as modulators of neuroinflammatory and synaptic processes in AD. However, heterogeneity in formulations, dosing, and study design limits firm conclusions. Future research should focus on dose optimization, biomarker-guided clinical trials, and long-term safety assessments to better define their therapeutic potential in AD.”

https://pubmed.ncbi.nlm.nih.gov/42211879

“The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.”

 “cannabinoids should be viewed as pleiotropic modulators of AD-relevant processes rather than as agents acting through a single unified mechanism.”

“cannabinoid-derived compounds with combined receptor-mediated and intrinsic antioxidant properties may represent promising therapeutic candidates.”

https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2026.1833021/full

Emerging preclinical evidence supports a potential role for cannabidiol in the management of sickle cell disease

Posted on by

“Sickle cell disease (SCD) imposes a substantial global health burden, with acute and chronic pain representing a major component of morbidity. Standard pain management, largely opioid-based, carries significant risks and often provides inadequate long-term relief, highlighting an unmet need for alternative analgesics as well as disease modifiers.

Medicinal cannabinoids have analgesic and antiinflammatory properties; most clinical studies so far have used Δ9-tetrahydrocannabinol (THC)-containing products with conflicting outcomes. In contrast, purified cannabidiol (CBD) has a broader spectrum of action beyond the endocannabinoid system, lacks psychoactive effects and associated long-term risks, allows safe dose optimization and can be prescribed legally in many settings.

Here, we review evidence for CBD’s potential analgesic and disease-modifying properties for management of SCD.

Pain in SCD arises from local tissue inflammation and neuroinflammation, compounded by abnormal pain modulation and pro-nociceptive CNS alterations. CBD may attenuate the pathophysiological processes of SCD by modulating pro-inflammatory immune pathways, reducing oxidative stress and suppression of neurogenic inflammation. CBD also has a direct inhibitory effect on afferent nociceptive pathways. Furthermore, CBD has an important pain-modulating role by suppressing excitatory mechanisms in the dorsal root ganglia and CNS. Additionally, CBD may modulate pain-processing brain networks and attenuate opioidinduced reward-seeking behavior.

Although human data are very limited, emerging preclinical findings and early patient reports offer cautious optimism for CBD as a therapeutic option with potential disease-modifying properties in SCD. Clinically meaningful benefits may be expected in specific patient subgroups, identifiable through well-designed clinical and mechanistic studies focused on pain processing and neuroinflammation.”

https://pubmed.ncbi.nlm.nih.gov/42206420

https://haematologica.org/article/view/14205

Cannabidiol alleviates chemotherapy-induced cognitive decline and neuropathology

Posted on by

“Chemotherapy is frequently associated with long-term cognitive impairments in cancer survivors that negatively impact their quality of life. Effective mitigation strategies for cancer therapy-related cognitive impairments (CRCI) are still underdeveloped. Our clinical studies on breast cancer patients treated with doxorubicin (Adriamycin®, ADR) and cyclophosphamide (CYP) found significant CRCI associated with neurodegenerative and neuroinflammatory signatures.

Current preclinical and clinical studies highlight the potential of cannabidiol (CBD) for alleviating cognitive deficits in neurodegenerative conditions.

For example, Epidiolex® is an FDA-approved 99% pure formulation of CBD for treating pediatric epilepsy. CBD, a non-psychoactive component of cannabis, is recognized for its neuroprotective and anti-inflammatory effects.

This study, using a mouse model of adjuvant chemotherapy (ADR and CYP)-induced cognitive decline, tested the efficacy of oral administration of 99% pure CBD (20 mg/kg) in sesame oil. ADR + CYP-treated mice receiving CBD for one month showed significant neurocognitive improvements in learning and memory, executive function, and memory consolidation tasks often impaired in cancer survivors. CBD treatment also restored brain endocannabinoid (ECB) levels and reduced ECB-metabolizing enzymes in vivo. Notably, CBD mitigated chemotherapy-induced loss of neurogenesis, neuronal plasticity, synaptic density, and elevated gliosis.

In summary, this data provides preclinical evidence for a translationally feasible approach to alleviate CRCI, an unmet medical need.”

https://pubmed.ncbi.nlm.nih.gov/42202974

“Oral administration of cannabidiol (CBD, 99% purity) formulation significantly ameliorated chemotherapy-induced cognitive impairments in learning, memory, executive function, and memory consolidation in mice.”

“CBD restored endocannabinoid signaling, reduced neuroinflammation, and preserved neurogenesis, synaptic plasticity, and neuronal integrity.”

“These results identify a translationally feasible CBD-based strategy to mitigate cancer therapy-related cognitive impairment in survivors.”

“Taken together, these findings provide convergent behavioral, molecular, and cellular evidence that oral administration of 99% pure CBD post-chemotherapy can ameliorate CRCI by normalizing ECB tone, reducing microglial and astrocytic activation, preserving synaptic integrity, restoring activity-dependent plasticity, and rescuing neurogenesis.

Considered alongside prior reports that stem cell therapies, BDNF augmentation, and cannabinoid or paracannabinoid agents can reverse neurotoxic treatment-related cognitive deficits, the present study positions CBD as a mechanistically informed, clinically accessible candidate for future trials targeting CRCI in cancer survivors.”

https://www.sciencedirect.com/science/article/pii/S0304383526003757?via%3Dihub

Solubility-improved and antitumor activity of (-)-cannabidiol conjugates

Posted on by

“Background: (-)-Cannabidiol (CBD) is a naturally occurring terpenoid belonging to the cannabinoid family, which is isolated from the Cannabis sativa L. plant. It possesses significant therapeutic potential, providing minimal side effects and no psychoactive activity. However, CBD applications are limited by a poor aqueous solubility and low bioavailability.

Objective: To address these limitations and investigate the impact of structural modification on solubility, we plan in this work the synthesis of a series of CBD conjugates along with the evaluation of their antitumor activity.

Methods: Conjugates are characterized by Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques, along with the solubility in water, glycerine, n-hexane and isooctane evaluated by High-Performance Liquid Chromatography (HPLC). The antitumoral activity of the CBD conjugates has been tested using cytotoxicity (IC50), cell migration and cell colony formation assays against lung adenocarcinoma cells A549.

Results: Specifically, oligo(ethylene glycol)-, alkyl- and L-valine-functionalized CBD derivatives are synthesized via selective esterification of its phenolic groups in good yields. Solubility profiles revealed a marked improvement compared to CBD. Notably, oligo(ethylene glycol) derivatives significantly enhanced solubility in water and glycerine, with 1b exhibiting a 14-fold increase in water solubility. The L-valine bis-conjugated derivative 4 also exhibited substantially improved solubility across all tested solvents, reaching up to a 13-fold increase in glycerine. In contrast, alkyl conjugates 2a,b showed only modest improvements. In addition, the in vitro evaluation against A549 revealed improved cytotoxic activity for 1a, 1b and 4 compared to native CBD, and with 1a additionally displaying antimigratory and colony formation inhibitory effects.

Conclusions: Collectively, our results highlight the critical role of conjugate structure in modulating physicochemical and biological properties of CBD and underscore the potential of these CBD conjugates as promising candidates for further pharmacological investigation and development.”

https://pubmed.ncbi.nlm.nih.gov/42210316

https://link.springer.com/article/10.1186/s42238-026-00453-5

Structural Characterization and Antioxidant Activity of a Crude Polysaccharide from Cannabis sativa Leaves

Posted on by

“As a traditional Chinese herbal medicine, Cannabis sativa holds broad prospects for application in the development of functional foods, pharmaceutical formulations, dietary supplements, and cosmetic products. However, the bioactivity of polysaccharides in C. sativa has been largely overlooked.

In this study, crude C. sativa leaf polysaccharide (CSLP) was extracted using the hot-water extraction and ethanol-precipitation method.

CSLP contains 64.15 ± 1.96% carbohydrates and 2.13 ± 0.47% protein, with a yield of 6.71 ± 0.84% (w/w). Preliminary structural characterization showed that CSLP was mainly composed of arabinose, galactose, and glucose, with a molecular weight of 28.867 kDa.

CSLP not only demonstrated potential in vitro antioxidant activity against ABTS, DPPH, superoxide anion, and hydroxyl radicals, but also repaired H2O2-induced oxidative damage in RAW 264.7 macrophages by increasing the cellular levels of SOD, CAT, and GSH-Px, and reducing MDA levels. Mechanistically, CSLP possibly modulated the Nrf2/Keap1 signaling pathway in H2O2-stimulated RAW 264.7 cells via upregulating the gene expressions of Nrf2, NQO1, and HO-1, while downregulating Keap1 expression.

These results suggest that CSLP could potentially be used as an antioxidant ingredient in the food, pharmaceutical, and cosmetic industries.”

https://pubmed.ncbi.nlm.nih.gov/42195853

“Hemp (Cannabis sativa L.), a member of the Cannabaceae family, is a plant with both medicinal and edible properties.”

“C. sativa and its extracts exhibit various bioactivities, showing broad application prospects in functional foods, pharmaceutical formulations, dietary supplements, and cosmetics.”

“These findings provide a theoretical foundation for the development of C. sativa leaf polysaccharides as natural antioxidants in the functional food and pharmaceutical sectors.”

https://www.mdpi.com/2304-8158/15/10/1649

Industrial and Therapeutic Applications of Hemp: A Review

Posted on by

“Hemp (Cannabis sativa L.) is a multipurpose crop with significant industrial and therapeutic potential.

This article reviews the various uses of hemp in production, building, food, cosmetics and medicine, focusing on its economic, environmental and health benefits.

Industrially, hemp has been used for making fabrics, paper, bioplastics, construction materials and biofuels, because of its strong fibres, fast growth and low impact on the environment.

Hemp seed oil and protein in the food and beauty industries are gaining more recognition for their nutritional and functional characteristics.

Medically, compounds extracted from hemp, especially cannabidiol (CBD) and other non-psychoactive phytochemicals, have been shown to possess significant anti-inflammatory, pain-relieving, neuroprotective, antioxidant and antibacterial properties.

This article talks about how better cultivation methods, processing technologies, and extraction techniques can help improve product quality, marketability, regulatory frameworks, safety standards and the quality control measures that are in place to monitor hemp production and utilization, as well as the focus on new policies in developing nations.

Even though hemp has a wide range of potentials, the industry still faces difficulties in the form of laws, lack of infrastructure, unequal product standardization, and lack of scientific proof in certain areas of application. This article further identifies research gaps and points out potential areas for innovation, policymaking, and market development to be explored in the future.

If backed up by proper regulations and research, hemp has great potential to contribute to the development of environmentally friendly industries, the improvement of public health and the socio-economic upliftment of communities.”

https://pubmed.ncbi.nlm.nih.gov/42197253

“Hemp (Cannabis sativa L.) was among the earliest plants cultivated by humans. Humans have been using it for fibre, food, and medicine for more than 10,000 years, as shown by archeological findings. To make ropes, textiles, paper and medicinal preparations, early civilisations in China, Mesopotamia, and Egypt used hemp. In ancient China, some of the first types of paper were made from hemp fibres. Besides that, traditional Chinese medicine in 2700 BCE described the healing effects of hemp-based remedies.” 

https://www.mdpi.com/1420-3049/31/10/1699

Antitumor Activity of Cannabinoids and Their Interaction with Chemotherapy: A Systematic Review and Meta-Analysis of Preclinical Evidence

Posted on by

“Background: Cannabinoids are studied as anticancer agents, but their effects vary across tumors, compounds, and experimental settings, underscoring the need to define consistent patterns. Our objective was to map cannabinoid efficacy across cancer preclinical models and identify tumor settings with the greatest translational promise. 

Methods: The protocol was registered on PROSPERO (CRD42025543744); PubMed, Embase, and CENTRAL were searched on 4 April 2024 for in vitro and in vivo studies assessing cannabinoid antitumor effects alone or with chemotherapy versus vehicle or chemotherapy only. Random-effects models yielded pooled mean differences (MD) with 95% confidence intervals (CI). MDs of viable cells were calculated for in vitro assays and tumor volume (mm3) for in vivo studies. Reports of various compounds, cannabidiol (CBD), tetrahydrocannabinol (THC) or synthetic cannabinoids, were pooled. 

Results: We included 189 studies in the final analysis. In vitro, cannabinoids reduced cell viability modestly overall, with significant effects in glioblastoma (MD -18.77 [CI: -27.15; -10.39]) and a nonsignificant trend in breast cancer (MD -6.75 [CI: -13.90; 0.40]). For in vivo, monotherapy showed the most consistent efficacy in glioblastoma, significantly reducing tumor volume by MD -980.58 mm3; [CI: -1270.2; -690.88]. Addition to temozolomide produced a favorable but nonsignificant decrease of MD -220.65 mm3; [CI: -579.34; 138.03, vs. temozolomide]. In breast cancer, cannabinoids achieved smaller yet significant tumor reductions (MD -402.64 mm3); [CI: -671.84; -133.45]. Synthetic agents had the largest effect (MD -1295.19 mm3); [CI: -1664.33; -928.05] -CBD plus doxorubicin vs. doxorubicin). Lung cancer (MD -562.17 mm3); [CI: -693.99; -430.35] and prostate cancer (MD -1136.59 mm3); [95% CI: -1320.97; -952.21] also had a significant response, whereas colon, pancreatic, and hepatocellular carcinoma models showed inconsistent or null responses. 

Conclusions: Cannabinoids show promise as adjuncts in oncotherapy, particularly in glioblastoma and breast cancer, to enhance chemotherapy efficacy. These findings should be interpreted with caution given the high inter-study heterogeneity typical of preclinical research and should be considered hypothesis-generating, warranting further validation in standardized and clinically relevant models.”

https://pubmed.ncbi.nlm.nih.gov/42198443

“Cannabinoids have attracted growing attention in oncology as both supportive agents and potential direct antitumor therapies.”

“Beyond symptom management, preclinical studies over the past two decades have demonstrated that exogenous cannabinoids can influence key hallmarks of cancer, including proliferation, apoptosis, angiogenesis, and metastasis.”

“Notably, multiple studies indicate that cannabinoids can act synergistically with chemotherapy or radiotherapy, amplifying antitumor effects while potentially attenuating treatment-related toxicity. These interactions are clinically appealing, as they suggest a capacity to sensitize tumor cells to conventional agents and possibly enable dose reductions that limit systemic adverse effects.”

“Cannabinoids show emerging potential as adjuncts in oncological treatment, with relatively consistent signals observed particularly in glioblastoma and breast cancer models.”

https://www.mdpi.com/1424-8247/19/5/768

Identification of Changes in the Transcriptome Profile of Human Hepatoma HepG2 Cells Exposed to Combined Sorafenib and Cannabis Treatment

Posted on by

“Cannabis-derived compounds are increasingly used as adjuncts in cancer therapy due to their reported antiproliferative and pro-apoptotic effects. However, potential drug-herb interactions with standard anticancer agents-namely sorafenib-remain unclear.

This study investigated the interaction between cannabis and sorafenib, together with transcriptomic alterations in human hepatoma HepG2 cells.

Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the Combenefit program. RNA sequencing was performed to characterize gene expression changes across treatment groups.

Combination analysis demonstrated concentration-dependent synergistic effects at intermediate doses. Transcriptomic profiling revealed that the combination treatment induced a broader and more distinct set of differentially expressed genes compared with single treatments.

Integrated enrichment analyses showed consistent activation of stress- and inflammation-related pathways, including tumor necrosis factor-α via nuclear factor-kappaB (TNF/NF-κB), mitogen-activated protein kinase (MAPK), janus kinase/signal transducers and activators of transcription (JAK-STAT), oxidative stress, and p53-mediated apoptosis, alongside suppression of metabolic and proliferative processes. While several pathways were shared across treatments, the combination group exhibited a more coordinated transcriptional response, including enrichment of integrated stress response, cytokine signaling, endoplasmic reticulum stress, and epigenetic regulation. These findings were supported by increased reactive oxygen species production and apoptosis, particularly in the combination group.

Overall, cannabis may potentiate sorafenib activity through enhanced cellular stress and anti-proliferative signaling.”

https://pubmed.ncbi.nlm.nih.gov/42196320

https://www.mdpi.com/1422-0067/27/10/4342

Medicinal smokes

Posted on by

“All through time, humans have used smoke of medicinal plants to cure illness.

To the best of our knowledge, the ethnopharmacological aspects of natural products’ smoke for therapy and health care have not been studied. Mono- and multi-ingredient herbal and non-herbal remedies administered as smoke from 50 countries across the 5 continents are reviewed. Most of the 265 plant species of mono-ingredient remedies studied belong to Asteraceae (10.6%), followed by Solanaceae (10.2%), Fabaceae (9.8%) and Apiaceae (5.3%).

The most frequent medical indications for medicinal smoke are pulmonary (23.5%), neurological (21.8%) and dermatological (8.1%).

Other uses of smoke are not exactly medical but beneficial to health, and include smoke as a preservative or a repellent and the social use of smoke.

The three main methods for administering smoke are inhalation, which accounts for 71.5% of the indications; smoke directed at a specific organ or body part, which accounts for 24.5%; ambient smoke (passive smoking), which makes up the remaining 4.0%.

Whereas inhalation is typically used in the treatment of pulmonary and neurological disorders and directed smoke in localized situations, such as dermatological and genito-urinary disorders, ambient smoke is not directed at the body at all but used as an air purifier.

The advantages of smoke-based remedies are rapid delivery to the brain, more efficient absorption by the body and lower costs of production.

This review highlights the fact that not enough is known about medicinal smoke and that a lot of natural products have potential for use as medicine in the smoke form. Furthermore, this review argues in favor of medicinal smoke extended use in modern medicine as a form of drug delivery and as a promising source of new active natural ingredients.”

https://pubmed.ncbi.nlm.nih.gov/17030480

“From time immemorial, human beings have used smoke of medicinal plants to lead a healthy life.”

https://www.sciencedirect.com/science/article/abs/pii/S0378874106004314?via%3Dihub

Impressive Impact of Hemp Extract on Antioxidant System in Honey Bee (Apis mellifera) Organism

Posted on by

“We examined the effect of hemp extract on the activity of the antioxidant system (catalase, peroxidase, glutathione, superoxide dismutase, and total antioxidant capacity) in the hemolymph of adult honey bees (Apis mellifera).

The bees were divided into three groups: (1) an experimental group fed with pure sugar syrup with cotton strips soaked with hemp extract put inside the cage; (2) an experimental group fed with a mixture of sugar syrup with hemp extract; and (3) a control group fed with a mixture of sugar and a water-glycerine solution. Hemolymph samples were collected on the 1st day of this study and then every week, until all bees in the group died.

The activities of all antioxidant enzymes were higher for the experimental groups, compared to those for the control group. The highest antioxidant activities were noted in the group supplemented with cannabis with the use of syringes. Supplementation with hemp also increased the lifespan of bees in this group compared to that of the bees consuming only sugar syrup (control: 35 days), with 49 and 52 days for groups of cannabis on strips and in syrup, respectively.

Hemp extract, thanks to its antioxidant properties, increased the activities of key antioxidant enzymes that protect the bee’s organisms against free radicals and thus delay the aging processes.”

https://pubmed.ncbi.nlm.nih.gov/35453392

“The aim of our research was to determine the effect of hemp extract on the activities of enzymes in the antioxidant system in bees’ hemolymph, along with the aging processes.”

“Hemp extract significantly increased the activity of antioxidant enzymes, extending the life of bees to 49 days (for the strip method) and 56 days (for the syringe method). In addition, we showed that a faster and stronger effect was obtained during supplementation in syrup in syringes, where the activities for the enzymes SOD, CAT, GPx, GST, and TAC were the highest.

Thanks to this, we believe that hemp extract can in the future contribute to the improvement of the natural immunity of honey bees and help them with the fight against environmental pollution and the increase of oxidative stress.”

https://www.mdpi.com/2076-3921/11/4/707