Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial

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Multiple Sclerosis (MS) is a prevalent inflammatory disease in which the immune system plays an essential role in the damage, inflammation, and demyelination of central nervous system neurons (CNS). The cannabinoid receptor type 2 (CB2) agonists possess anti-inflammatory effects against noxious stimuli and elevate the neuronal survival rate. We attempted to analyze the protective impact of low doses of β-Caryophyllene (BCP) in experimental autoimmune encephalomyelitis (EAE) mice as a chronic MS model. Immunization of female C57BL/6 mice was achieved through two subcutaneous injections into different areas of the hind flank with an emulsion that consisted of myelin Myelin oligodendrocyte glycoprotein (MOG)35–55 (150 µg) and complete Freund’s adjuvant (CFA) (400 µg) with an equal volume. Two intraperitoneal (i.p.) injections of pertussis toxin (300 ng) were performed on the animals on day zero (immunizations day) and 48 h (2nd day) after injection of MOG + CFA. The defensive effect of low doses of BCP (2.5 and 5 mg/kg/d) was investigated in the presence and absence of a CB2 receptor antagonist (1 mg/kg, AM630) in the EAE model. We also examined the pro/anti-inflammatory cytokine levels and the polarization of brain microglia and spleen lymphocytes in EAE animals. According to our findings, low doses of BCP offered protective impacts in the EAE mice treatment in a CB2 receptor-dependent way. In addition, according to results, BCP decreased the pathological and clinical defects in EAE mice via modulating adaptive (lymphocytes) and innate (microglia) immune systems from inflammatory phenotypes (M1/Th1/Th17) to anti-inflammatory (M2/Th2/Treg) phenotypes. Additionally, BCP elevated the anti-inflammatory cytokine IL-10 and reduced blood inflammatory cytokines. BCP almost targeted the systemic immune system more than the CNS immune system. Thus, a low dose of BCP can be suggested as a therapeutic effect on MS treatment with potent anti-inflammatory effects and possibly lower toxicity.

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The Skin and Natural Cannabinoids–Topical and Transdermal Applications

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The chemical constituents of the Cannabis plant known as cannabinoids have been extensively researched for their potential therapeutic benefits. The use of cannabinoids applied to the skin as a potential method for both skin-related benefits and systemic administration has attracted increasing interest in recent years. This review aims to present an overview of the most recent scientific research on cannabinoids used topically, including their potential advantages for treating a number of skin conditions like psoriasis, atopic dermatitis, and acne. Additionally, with a focus on the pharmacokinetics and security of this route of administration, we investigate the potential of the transdermal delivery of cannabinoids as a method of systemic administration. The review also discusses the restrictions and difficulties related to the application of cannabinoids on the skin, emphasizing the potential of topical cannabinoids as a promising route for both localized and systemic administration. More studies are required to fully comprehend the efficacy and safety of cannabinoids in various settings.

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The pharmacology and therapeutic role of cannabidiol in diabetes

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In recent years, cannabidiol (CBD), a non-psychotropic cannabinoid, has garnered sub- stantial interest in drug development due to its broad pharmacological activity and multi-target effects. Diabetes is a chronic metabolic disease that can damage multiple organs in the body, leading to the development of complications such as abnor- mal kidney function, vision loss, neuropathy, and cardiovascular disease. CBD has demonstrated significant therapeutic potential in treating diabetes mellitus and its com- plications owing to its various pharmacological effects. This work summarizes the role of CBD in diabetes and its impact on complications such as cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy. Strategies for discovering molecular targets for CBD in the treatment of diabetes and its complications are also proposed. Moreover, ways to optimize the structure of CBD based on known targets to generate new CBD analogues are explored.

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Cannabis for the treatment of amyotrophic lateral sclerosis: What is the patients’ view?

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Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the “real-life” situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported “rational” consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.

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THC-O-Acetate: Scarce Evidence for a Psychedelic Cannabinoid

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There is a growing interest in semi-synthetic cannabinoids, including THC-O-acetate (THC-Oac). Some cannabis marketers and users have claimed that THC-Oac produces psychedelic effects; the current study is the first to examine this claim. Researchers developed an online survey for THC-Oac consumers based on previous cannabis and psychedelic use surveys and in consultation with the moderator of an online forum. The survey assessed the experiential profile of THC-Oac and included items from the Mystical Experience Questionnaire (MEQ), an instrument for assessing psychedelic experiences. Participants reported a low to moderate level of cognitive distortions (altered sense of time, difficulties concentrating, difficulties with short-term memory) and few visuals or hallucinations. Participants’ responses were significantly below the threshold for a complete mystical experience on all four MEQ dimensions. Participants who had used classic (5-HT2A agonist) psychedelics had lower scores on all MEQ dimensions. When asked directly, 79% responded that using THC-Oac is “not at all” or “a little” of a psychedelic experience. Some reports of psychedelic experiences may be due to expectations or contaminants. Those having prior experience with classic psychedelics had lower ratings of mystical experiences.

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A comparison of advertised versus actual cannabidiol (CBD) content of oils, aqueous tinctures, e-liquids and drinks purchased in the UK

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To evaluate the efficacy and safety of cannabidiol (CBD) for the treatment of epilepsy in a real-world setting.
In this retrospective observational study, we included PwE with epilepsy who received a prescription for CBD between 01.03.2019 and 30.11.2022 and had a follow-up period ≥ 3 months. Participants were evaluated at baseline and after 3, 6, and 12 months. “Responders” were defined as individuals experiencing a reduction in seizure frequency > 30% but < 80% compared to baseline, while "super responders" were those with a reduction ≥ 80%. Adverse events were recorded to assess safety.

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Real-world experience with cannabidiol as add-on treatment in drug-resistant epilepsy

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To evaluate the efficacy and safety of cannabidiol (CBD) for the treatment of epilepsy in a real-world setting.
In this retrospective observational study, we included PwE with epilepsy who received a prescription for CBD between 01.03.2019 and 30.11.2022 and had a follow-up period ≥ 3 months. Participants were evaluated at baseline and after 3, 6, and 12 months. “Responders” were defined as individuals experiencing a reduction in seizure frequency > 30% but < 80% compared to baseline, while "super responders" were those with a reduction ≥ 80%. Adverse events were recorded to assess safety.

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The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study

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Anxiety is a condition for which current treatments are often limited by adverse events (AEs). Components of medicinal cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC), have been proposed as potential treatments for anxiety disorders, specifically posttraumatic stress disorder (PTSD). To evaluate quality-of-life outcomes after treatment with various cannabis formulations to determine the effectiveness and associated AEs.

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Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt

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Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches.
Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups

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Therapeutic Potential and Predictive Pharmaceutical Modeling of Stilbenes in Cannabis sativa

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Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds.

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Cannabinoid contents in hemp teas and estimation of their transfer into tea infusions

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This study focused on the investigation of cannabinoid profiles and contents of 23 different
hemp teas and on the individual transfer of 16 cannabinoids from hemp teas into their tea
infusions. The total cannabinoid content in the dry products averaged 14,960mg kg1, with
CBD&CBDA (sum of cannabidiol (CBD) and cannabidiolic acid (CBDA)) being the major compo-
nent, accounting for 87% of the total cannabinoid content. The D9-tetrahydrocannabinol (D9- 11 1
THC) content ranged from 16mg kg to 935mg kg and was on average 221mg kg . For each hemp tea, an infusion was prepared according to a standardized protocol issued by the German Standardisation body DIN and transfer rates per cannabinoid were estimated by com- paring the contents in the dry material with the concentrations in the aqueous infusion. The limited water solubility of cannabinoids results in limited extraction efficiency for cannabinoids using boiling water to prepare a tea infusion and the average transfer rate of the psychoactive D9-THC was only 0.5%.

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The role of cannabidiol in aging

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Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.

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