“Psoriasis is a chronic skin condition that can significantly impact the quality of life of those affected. As an autoimmune disease, it can lead to itchy, painful, and scaly patches on the skin. Although various treatments, including topical creams, phototherapy, and systemic medications, are currently available, they may not always offer effective relief and can have side effects. Researchers have thus been exploring the potential benefits of non-psychoactive compounds such as CBD, found in Cannabis sativa plants, for treating psoriasis. CBD treatment may reduce inflammation, oxidative stress, itching, abnormal proliferation of keratinocytes, and may increase hydration. This review aims to provide an overview of the existing literature on the potential uses of CBD for psoriasis treatment.”
“Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients’ satisfaction in MS patients treated with nabiximols as monotherapy.
Methods: To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response. The following data were collected at treatment start (baseline) and 12 weeks thereafter: Modified Ashworth scale (MAS), scores at numerical rating scales ranging from 0 (absent) to 10 (considerable) for effect on spasticity (sNRS), pain (pNRS), gait (gNRS), urinary symptoms (uNRS), tolerability (tNRS) as assessed by the treating neurologist, and overall treatment satisfaction (TsNRS) and tolerability (tNRS) as assessed by the patient.
Results: Ninety-five patients (44 relapsing remitting, 37 secondary progressive and 14 primary progressive MS; median age = 53 (IQR 45-62); female 70%; median EDSS 6 (IQR 4-6), concomitant antispastic treatments in 54% of patients) were included. From baseline to week 12, median MAS score decreased from 3.0 to 2.0 (p < 0.001). Median scores of the each NRS also significantly decreased (p < 0.001 for all comparisons). At week 12, the median TsNRS and tTS scores were 8/10 (IQR: 6-9) and 9/10 (IQR: 7-10), respectively, and 93.7% of patients continued to use nabiximols at the average dose of six sprays/day. No clinical factors, including use of nabiximols as add on vs. monotherapy, were associated with responder status.
Conclusions: Our first Swiss, multicentric, observational, real-life study supports and enhances previous finding of nabiximols as monotherapy and as add-on therapy, being an effective, safe and well-tolerated treatment option for resistant MS spasticity and spasticity-related symptoms (pain, bladder dysfunction and gait).”
“Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination and axonal loss. Cannabis, an immunomodulating agent, is known for its ability to treat MS effectively. However, due to variations in the profile of secondary metabolites, especially cannabinoids, among cannabis cultivars, the effectiveness of cannabis treatment can vary, with significant variability in the effects on different biological parameters. For screening available cultivars, cellular in vitro as well as pre-clinical in vivo assays, are required to evaluate the effectiveness of the wide range of chemical variability that exists in cannabis cultivars. This study evaluated comparatively three chemically diverse cannabis cultivars, CN2, CN4 and CN6, containing different ratios of phytocannabinoids, for their neuroinflammatory activity in MS model.
Materials and methods: In vitro experiments were performed with lipopolysaccharide (LPS)-activated BV-2 microglia and primary glial cells to evaluate the effect of different cannabis cultivars on nitric oxide (NO) and inflammatory cytokines, as well as inducible nitric oxide synthase (iNOS) protein expression. An in vivo experiment using the experimental autoimmune encephalomyelitis (EAE) MS model was conducted using Myelin oligodendrocyte glycoprotein (MOG) as the activating peptide. The cannabis extracts of the cultivars CN2, CN4, CN6 or vehicle, were intraperitoneally injected with clinical scores given based on observed symptoms over the course of study. At the end of the experiment, the mice were sacrificed, and splenocyte cytokine secretion was measured using ELISA. Lumbar sections from the spinal cord of treated MS mice were evaluated for microglia, astrocytes and CD4+ cells.
Results: Extracts of the CN2 cultivar contained tetrahydrocannabinolic acid (THCA) and tetrahydrocannabinol (THC) without cannabidiol (CBD), and a number of monoterpenes. CN4 contained cannabidiolic acid (CBDA) and tetrahydrocannabidiolic acid (THCA), with significant amounts of THC: CBD in a 1:1 ratio, as well as sesquiterpenes and some monoterpenes; and CN6 contained primarily CBDA and THCA, as well as THC and CBD in a 2:1 ratio, with some sesquiterpenes and no monoterpenes. All extracts were not cytotoxic in glial cells up to 50 µg/ml. Dose dependent inhibition of LPS-induced BV2 as well as primary microglial NO secretion confirmed the anti-inflammatory and anti-oxidative activity of the three cannabis cultivars. CN2 but not CN4 reduced both astrocytosis and microglial activation in lumbar sections of EAE mice. In contrast, CN4 but not CN2 significantly decreased the secretion of TNFα and Interferon γ (IFNγ) in primary splenocytes extracted from EAE mice.
Conclusions: While both cannabis cultivars, CN2 and CN4, significantly reduced the severity of the clinical signs throughout the course of the study, they modulated different inflammatory mediators and pathways, probably due to differences in their phytocannabinoid composition. This demonstrates the differential potential of cannabis cultivars differing in chemotype to regulate neuroinflammation and their potential to treat MS.”
“Introduction: Whilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR).
Method: Patients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant.
Results: 141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %).
Conclusions: This preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design.”
“Cannabis-based medicinal products were prescribed to those with multiple sclerosis.•Significant improvements were observed in health-related quality of life. •Treatment was well-tolerated over the course of 6 months.”
“In recent years, the medical use of cannabinoids has attracted growing attention worldwide. In particular, anti-inflammatory properties of cannabinoids led to their emergence as potential therapeutic options for autoimmune and inflammatory disorders.
Recent studies have also shown that cannabinoid receptors are widely expressed and have endogenous ligands in the skin, suggesting that the skin has its own endocannabinoid system. The aim of this review is to discuss the potential therapeutic effects of cannabinoids in autoimmune and inflammatory skin diseases.
Following an overview of cannabinoids and the endocannabinoid system, we describe the cellular and molecular mechanisms of cannabinoids in skin health and disease. We then review the clinical studies of cannabinoids in autoimmune and inflammatory skin diseases including systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (Pso) and atopic dermatitis (AD). A primary literature search was conducted in July 2023, using PubMed and Web of Science. A total of 15 articles were included after excluding reviews, non-human studies and in vitro studies from 389 non-duplicated articles.
Available evidence suggests that cannabinoids may be beneficial for SSc, DM, Pso and AD. However, further studies, ideally randomized controlled trials, are needed to further evaluate the use of cannabinoids in autoimmune and inflammatory skin diseases.”
“The available data support the safety and efficacy of cannabinoids in SSc, DM, Pso and AD, as well as highlight the need for further studies to confirm their therapeutic use. In conclusion, available evidence suggests that cannabinoids have the potential therapeutic benefit with good tolerability in SSc, DM, Pso and AD. “
“Background: Cannabidiol (CBD), one major nonintoxicating phytocannabinoid from Cannabis sativa demonstrated anti-inflammatory effects in animal models of several inflammatory conditions, including arthritis. However, it is still unknown which cell types mediate these anti-inflammatory effects of CBD, and, since CBD binds to a plethora of receptors and enzymes, it is complicated to pinpoint its mechanism of action. In this study, we elucidate the effects of CBD on B cells and peripheral blood mononuclear cells (PBMCs) in respect to survival, calcium mobilization, drug uptake, and cytokine (IL-6, IL-10, and TNF) and immunoglobulin production.
Methods: Modulation of intracellular calcium and drug uptake in B cells was determined by using the fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin production was evaluated by enzyme-linked immunosorbent assay. PBMC composition and B cell survival after CBD treatment was assessed by flow cytometry.
Results: B cells express two major target receptors for CBD, TRPV2 (transient receptor potential vanilloid 2) and TRPA1 (transient receptor potential ankyrin 1), which are not regulated by B cell activation. CBD increased intracellular calcium levels in mouse and human B cells, which was accompanied by enhanced uptake of PoPo3. These effects were not dependent on transient receptor potential channel activation. CBD increased the number of early apoptotic B cells at the expense of viable cells and diminished interleukin (IL)-10 and tumor necrosis factor (TNF) production when activated T cell independently. In PBMCs, CBD increased IL-10 production when B cells were activated T cell dependent, while decreasing TNF levels when activated T cell independently. In PBMC/rheumatoid synovial fibroblast cocultures, CBD reduced IL-10 production when B cells were activated T cell independently. Immunoglobulin M production was augmented by CBD when B cells were activated with CpG.
Conclusion: CBD is able to provide pro- and anti-inflammatory effects in isolated B cells and PBMCs. This is dependent on the activating stimulus (T cell dependent or independent) and concentration of CBD. Therefore, CBD might be used to dampen B cell activity in autoimmune conditions such as rheumatoid arthritis, in which B cells are activated by specific autoantigens.”
“Multiple sclerosis (MS) is known as an autoimmune disease that damages the neurons in the central nervous system. MS is characterized by its most common symptoms of spasticity, muscle spasms, neuropathic pain, tremors, bladder dysfunction, dysarthria, and some intellectual problems, including memory disturbances. Several clinical studies have been conducted to investigate the effects of cannabis on the relief of these symptoms in MS patients. The efficacy of Cannabis sativa (C. Sativa) in the management of MS outcomes such as spasticity, pain, tremors, ataxia, bladder functions, sleep, quality of life, and adverse effects were assessed in this review.
Most clinical studies showed the positive effects of cannabinoids with their different routes of administration, such as oromucosal spray and oral form, in reducing most MS symptoms. The oromucosal spray Nabiximols demonstrated an improvement in reducing MS spasticity, pain, and quality of life with a tolerated adverse effect. Oral cannabinoids are significantly effective for treating MS pain and spasticity, while the other symptoms indicate slight improvement and the evidence is quite inconsistent. Oromucosal spray and oral cannabis are mainly used for treating patients with MS and have positive effects on treating the most common symptoms of MS, such as pain and spasticity, whereas the other MS symptoms indicated slight improvement, for which further studies are needed.”
“Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by the progressive death of motor neurons. Cannabidiol, the second most prevalent cannabinoid in the Cannabis sativa plant, is a potential therapeutic tool for ALS due to its antioxidant, anti-inflammatory, and anti-spasticity effects, as well as its complementary role in treating other neurodegenerative diseases. In SOD1-G93A murine ALS models, cannabinoids have been shown to slow disease progression, extending lifespan and increasing motor function. However, the effects of specific cannabinoids-including cannabidiol-are yet undefined and their functions slowing disease progression are unknown. To advance this understanding we aim to study the effects of cannabidiol treatment in a Caenorhabditis elegans ALS model: a SOD-1 mutant transgenic strain with SOD-1 aggregation in muscular cells. We will use a death assay to measure the lifespan of SOD-1 mutant C. elegans and cannabidiol-treated SOD-1 mutant C. elegans to investigate whether treatment with cannabidiol impacts the lifespan of SOD-1 mutants. To assess mechanosensation, we will touch C. elegans with sutures of various sizes, based on the Von Frey filaments touch response assay in humans. We will develop a novel computational analysis system to measure C. elegans movement in response to touch. We will then compare the motor response of the SOD-1 mutant transgenic strain to wild type and study if cannabidiol modulates a possible change in motor response. This study will evaluate the functions of cannabidiol as a potential therapeutic tool in ALS using a SOD-1 mutant C. elegans model.”
“Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.”
“Background and purpose: Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ9 -Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied.
Experimental approach: By using oligodendroglia-specific reporter mouse lines in combination with two models of toxin-induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination.
Key results: We show that THC administration enhanced oligodendrocyte regeneration, white matter remyelination and motor function recovery. THC also promoted axonal remyelination in organotypic cerebellar cultures. THC remyelinating action relied on the induction of oligodendrocyte precursor differentiation upon cell cycle exit and via CB1 cannabinoid receptor activation.
Conclusions and implications: Overall, our study identifies THC administration as a promising pharmacological strategy aimed to promote functional CNS remyelination in demyelinating disorders.”
