“Background: Few studies have reported on the use of cannabinoid products to treat hair loss.
Aim: This article aims to reconcile cannabinoids’ impact on hair growth.
Method: A comprehensive and structured search was conducted in PubMed and Google Scholar on 23 June 2022.
Result: While cannabidiol (CBD), a phytocannabinoid, may cause hair growth, several other phytocannabinoids may lead to hair loss. Additionally, the effect of CBD on hair growth may be concentration-dependent. CBD may cause hair loss at high concentrations (≥10 μM). Therefore, the concentration of CBD needs to be adjusted so that it is optimal for hair growth. One trial found that once-daily application of CBD-rich topical cannabis extract for six months increased nonvellus hair count by approximately 93.5% in 35 Caucasian AGA patients: 28 males aged 28-72 years [average 43 years] and 7 females aged 46-76 years [average 61 years]. Each application contained 3-4 mg of CBD. The CBD-rich topical cannabis extract was prepared by ultra-pulverizing Cannabis sativa [hemp] flower into a green chalk-like powder [10.78% CBD and 0.21% tetrahydrocannabinol] and then infusing the powder into a lanolin paste and Emu oil carrier.
Conclusion: Topical CBD preparations require further studies to establish their safety and efficacy profile. An ideal topical cannabinoid preparation should contain CBD at the right concentration and lack phytocannabinoid adulterants.”
“Background: Atopic dermatitis (AD) is one of the most common cutaneous inflammatory and pruritic diseases in dogs. Considering its multifactorial nature, AD can be a challenging disease to manage, and the therapeutic strategy must often be multimodal. In recent years, research has been moving toward the use of natural products which have beneficial effects on inflammation and itching, and no side effects. Cannabinoid receptors have been demonstrated to be expressed in healthy and diseased skin; therefore, one of the potential alternative therapeutic targets for investigating AD is the endocannabinoid system (ECS).
Objective: To immunohistochemically investigate the expression of the cannabinoid receptor type 2 (CB2R), and the cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in mast cells (MCs), macrophages, dendritic cells (DCs), T cells, and neutrophils of the skin of dogs with AD.
Animals: Samples of skin tissues were collected from eight dogs with AD (AD-dogs).
Materials and methods: The immunofluorescent stained cryosections of the skins of 8 dogs with AD having antibodies against CB2R, GPR55, TRPV1, TRPA1 were semiquantitatively evaluated. The inflammatory cells were identified using antibodies against tryptase (mast cells), ionized calcium binding adaptor molecule 1 (IBA1) (macrophages/DCs), CD3 (T cells), and calprotectin (neutrophils). The proportions of MCs, macrophages/DCs, T cells, and neutrophils expressing CB2R, GPR55, TRPV1 and TRPA1 were evaluated.
Results: The cells of the inflammatory infiltrate showed immunoreactivity (IR) for all or for some of the cannabinoid and cannabinoid-related receptors studied. In particular, MCs and macrophages/DCs showed CB2R-, GPR55-, TRPA1-, and TRPV1-IR; T cells showed CB2R-, GPR55- and TRPA1-IR, and neutrophils expressed GPR55-IR. Co-localization studies indicated that CB2R-IR was co-expressed with TRPV1-, TRPA1-, and GPR55-IR in different cellular elements of the dermis of the AD-dogs.
Conclusions and clinical importance: Cannabinoid receptor 2, and cannabinoid-related receptors GPR55, TRPV1 and TRPA1 were widely expressed in the inflammatory infiltrate of the AD-dogs. Based on the present findings, the ECS could be considered to be a potential therapeutic target for dogs with AD, and may mitigate itch and inflammation.”
“The evidence regarding the effect of cannabinoid and cannabinoid-related receptors on MCs, macrophages and DCs (CB2R, GPR55, TRPV1, TRPA1), T-cells (CB2R, GPR55, TRPA1), and on neutrophils (GPR55) suggests the possibility that the manipulation of the inflammatory cell functions with endocannabinoids and cannabinoids could result in a novel approach to the treatment of AD. Phytocannabinoids could potentially modulate inflammatory responses by regulating more than one underlying mechanism (inflammatory cells, keratinocytes, sensory nerves, fibroblasts, etc.).”
“The purpose of this study was to evaluate the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract (CSE) and its main constituents, cannabidiol and β-caryophyllene. An in vitro model of glutamate-induced neuronal excitotoxicity using SH-SY5Y cells was optimized. The impact of CSE on glutamate-impaired cell viability, brain-derived neurotrophic factor release, CB1 protein expression, and ERK levels was evaluated. The involvement of CB1 modulation was verified by the cotreatment with the CB1 antagonist AM4113. CSE was able to significantly protect SH-SY5Y from glutamate-impaired cell viability, and to counteract the changes in brain-derived neurotrophic factor levels, with a mechanism of action involving ERK modulation. Moreover, CSE completely reversed the reduction of CB1 receptor expression induced by glutamate, and the presence of the CB1 antagonist AM4113 reduced CSE effectiveness, suggesting that CBr play a role in the modulation of neuronal excitotoxicity. This work demonstrated the in vitro effectiveness of CSE as a neuroprotective agent, proposing the whole cannabis phytocomplex as a more effective strategy, compared to its main constituents alone, and suggested further investigations by using more complex cell models before moving to in vivo studies.”
“In the wide range of products containing hemp ingredients, cannabinoid oils are the most popular. They have gained popularity not only among people struggling with various health ailments, but also those who search for a neutral way of taking care of their body and mind.
The antioxidant activities of cannabinoid oils differing in the type of their main cannabinoid [i.e., Cannabigerol (CBG), Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (Δ9-THC), Cannabigerolic acid (CBGA), Cannabidiolic acid (CBDA) or Δ9-Tetrahydrocannabinolic acid (Δ9-THCA)] are compared and discussed in the paper. The oils with the same concentration of their main cannabinoid but prepared in different ways were applied in the experiments.
Following the presented results, cannabinoid oils obtained from the plant extracts are characterized by evidently greater antioxidant activity than those prepared from pure cannabinoids. The essential difference in the antioxidant activity of the oils containing the neutral or acidic form of a given cannabinoid is observed only in the case of THC and THCA oils.”
“Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide. In particular, the polar fraction of hemp including many phenolic compounds has been overlooked when compared with the more lipophilic fraction containing cannabinoids. Therefore, the aim of this study was to assess two extracts of industrial hemp (C. sativa) of different polarity (aqueous and hexane) by evaluating their antioxidant profile and their neuroprotective potential on pharmacological targets in the central nervous system (CNS). Several assays on in vitro antioxidant capacity (DPPH, superoxide radical, FRAP, ORAC), as well as inhibition of physiological enzymes such as acetylcholinesterase (AChE) and monoaminooxidase A (MAO-A) were carried out in order to find out how these extracts may be helpful to prevent neurodegenerative disorders. Neuro-2a cell line was selected to test the cytotoxic and neuroprotective potential of these extracts. Both extracts showed striking antioxidant capacity in the FRAP and ORAC assays, particularly the hexane extract, and interesting results for the DPPH and superoxide radical uptake assays, with the aqueous extract standing out especially in the latter. In enzyme inhibition assays, the aqueous extract showed AChE and MAO-A inhibitory activity, while the hexane extract only reached IC50 value for AChE inhibitory bioassay. Neuro-2a assays demonstrated that polyphenolic extract was not cytotoxic and exhibited cytoprotective properties against hydrogen peroxide and antioxidant response decreasing reactive oxygen species (ROS) production. These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders.”
“In conclusion, this study provided new insights into the biological activities of two different extracts of C. sativa. It was revealed that these extracts constitute a valuable and interesting natural source of bioactive molecules with great antioxidant properties, potentially capable of preventing neurodegenerative diseases.”
“Cannabis plant has been used from ancient times with therapeutic purposes for treating human pathologies, but the identification of the cellular and molecular mechanisms underlying the therapeutic properties of the phytocannabinoids, the active compounds in this plant, occurred in the last years of the past century.
In the late 1980s and early 1990s, seminal studies demonstrated the existence of cannabinoid receptors and other elements of the so-called endocannabinoid system. These G protein-coupled receptors (GPCRs) are a key element in the functions assigned to endocannabinoids and appear to serve as promising pharmacological targets. They include CB1, CB2, and GPR55, but also non-GPCRs can be activated by endocannabinoids, like ionotropic receptor TRPV1 and even nuclear receptors of the PPAR family.
Their activation, inhibition, or simply modulation have been associated with numerous physiological effects at both central and peripheral levels, which may have therapeutic value in different human pathologies, then providing a solid experimental explanation for both the ancient medicinal uses of Cannabis plant and the recent advances in the development of cannabinoid-based specific therapies.
This chapter will review the scientific knowledge generated in the last years around the research on the different endocannabinoid-binding receptors and their signaling mechanisms. Our intention is that this knowledge may help readers to understand the relevance of these receptors in health and disease conditions, as well as it may serve as the theoretical basis for the different experimental protocols to investigate these receptors and their signaling mechanisms that will be described in the following chapters.”
“The wide distribution of the endocannabinoid system (ECS) throughout the body and its pivotal pathophysiological role offer promising opportunities for the development of novel therapeutic drugs for treating several diseases. However, the need for strategies to circumvent the unwanted psychotropic and immunosuppressive effects associated with cannabinoid receptor agonism/antagonism has led to considerable research in the field of molecular alternatives, other than type-1 and type-2 (CB1/2) receptors, as therapeutic targets to indirectly manipulate this pro-homeostatic system. In this context, the use of selective inhibitors of proteins involved in endocannabinoid (eCB) transport and metabolism allows for an increase or decrease of the levels of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) in the sites where these major eCBs are indeed needed. This chapter will briefly review some preclinical and clinical evidence for the therapeutic potential of ECS pharmacological manipulation.”
“Background: Cannabidiol (CBD) is a non-psychoactive phytocannabinoid constituent of Cannabis sativa with pain-relieving and anti-inflammatory properties. With the emphasis on natural ingredients in cosmetics, CBD has become a new cosmetic ingredient due to its ability to alleviate inflammation. However, in-depth studies that directly compare the effective mechanism and the therapeutic potential of CBD are still needed.
Purpose: The aim of the present study was to investigate the anti-inflammatory effect of CBD in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and compare it to dexamethasone (DEX).
Methods: RAW264.7 macrophages in the logarithmic growth phase were incubated in the presence or absence of LPS. After that, the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured. A luciferase reporter assay for nuclear factor kappa B (NF-κB) was performed, and the phosphorylation levels of the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways were measured.
Results: The present study indicated that CBD had a similar anti-inflammatory effect to DEX by attenuating the LPS-induced production of NO, IL-6, and TNF-α. However, only CBD attenuated JNK phosphorylation levels, and only DEX attenuated IKK phosphorylation levels.
Conclusion: These results suggested that CBD and DEX exhibit similar anti-inflammatory effects on LPS-induced RAW264.7 macrophages mainly through suppressing the MAPK and NF-κB signaling pathways, but with different intracellular mechanisms. These findings suggested that CBD may be considered a natural anti-inflammatory agent for protecting skin from immune disorders.”
“As alternative and complementary therapies grow in dermatology, plant extracts such as CBD have garnered significant attention in dermatology. The present study provided new insight of CBD against LPS-induced inflammation. Our results suggested that CBD and DEX suppress the LPS-induced activation of the MAPK and NF-κB signaling pathways in RAW264.7 cells through different intracellular components, indicating that the anti-inflammatory biological mechanism of CBD is different from other immuno-suppressants. Because macrophages exert various pro-inflammatory functions through multiple intracellular pathways, further in vivo and in vitro studies are necessary to enrich the theoretical knowledge of CBD and promote its future clinical application.”
“Endocannabinoid (eCB) signaling is markedly decreased in the hippocampus (Hip) of aged mice, and the genetic deletion of the cannabinoid receptor type 1 (CB1) leads to an early onset of cognitive decline and age-related histological changes in the brain. Thus, it is hypothesized that cognitive aging is modulated by eCB signaling through CB1.
In the present study, we detailed the changes in the eCB system during the aging process using different complementary techniques in mouse brains of five different age groups, ranging from adolescence to old age.
Our findings indicate that the eCB system is most strongly affected in middle-aged mice (between 9 and 12 months of age) in a brain region-specific manner. We show that 2-arachidonoylglycerol (2-AG) was prominently decreased in the Hip and moderately in caudate putamen (CPu), whereas anandamide (AEA) was decreased in both CPu and medial prefrontal cortex along with cingulate cortex (mPFC+Cg), starting from 6 months until 12 months. Consistent with the changes in 2-AG, the 2-AG synthesizing enzyme diacylglycerol lipase α (DAGLα) was also prominently decreased across the sub-regions of the Hip.
Interestingly, we found a transient increase in CB1 immunoreactivity across the sub-regions of the Hip at 9 months, a plausible compensation for reduced 2-AG, which ultimately decreased strongly at 12 months. Furthermore, quantitative autoradiography of CB1 revealed that [3H]CP55940 binding markedly increased in the Hip at 9 months. However, unlike the protein levels, CB1 binding density did not drop strongly at 12 months and at old age. Furthermore, [3H]CP55940 binding was significantly increased in the lateral entorhinal cortex (LEnt), starting from the middle age until the old age.
Altogether, our findings clearly indicate a middle-age crisis in the eCB system, which could be a potential time window for therapeutic interventions to abrogate the course of cognitive aging.”
“In conclusion, our observations indicate that the eCB system is most affected during the middle age in a brain region-specific manner. Taken together, the middle-age crisis in the eCB signaling corresponds well with the onset of neuroinflammatory glial activity and cognitive deficits in mice. We now hypothesize that late middle-age is the time period when a therapy based on the activation of the cannabinoid system has the highest efficacy to prevent cognitive aging and pathologies related to brain aging.”
“Antibiotics are used as the first line of treatment for bacterial infections. However, antibiotic resistance poses a significant threat to the future of antibiotics, resulting in increased medical costs, hospital stays, and mortality. New resistance mechanisms are emerging and spreading globally, impeding the success of antibiotics in treating common infectious diseases.
Recently, phytocannabinoids have been shown to possess antimicrobial activity on both Gram-negative and Gram-positive bacteria. The therapeutic use of phytocannabinoids presents a unique mechanism of action to overcome existing antibiotic resistance.
Future research must be carried out on phytocannabinoids as potential therapeutic agents used as novel treatments against resistant strains of microbes.”
“Current antibiotic treatments have limited efficacy against multidrug-resistant bacteria, causing a significant challenge for prescribing physicians. A lack of effective therapies or new antibiotics requires the development of alternative antimicrobial therapies. Research has shown phytocannabinoids and CB2 agonists to exhibit antibiotic activity against a variety of Gram-positive and Gram-negative bacteria. Although their antimicrobial activity is limited in terms of Gram-negative bacteria, they offer therapeutic potential when administered as an adjunct treatment with an outer membrane perturbing molecule to facilitate the permeation of compounds that are effective on Gram-positive bacteria. Research has also shown synergy supporting the potential for combination therapy both in vivo and in vitro. Furthermore, CB2 agonists, such as β-caryophyllene, are widely used in industry as food additives and traditional medicine, and many are FDA approved and generally recognised as safe (GRAS), making them a good option for a novel therapeutic. The studies presented in this review suggest an attractive potential for cannabinoid-based antibacterial treatments.”
