α-Pinene: A never-ending story

Phytochemistry“α-Pinene represents a member of the monoterpene class and is highly distributed in higher plants like conifers, Juniper ssp. and Cannabis ssp.

α-Pinene has been used to treat respiratory tract infections for centuries. Furthermore, it plays a crucial role in the fragrance and flavor industry. In vitro assays have shown an enantioselective profile of (+)- and (-)-α-pinene for antibacterial and insecticidal activity, respectively.”

https://pubmed.ncbi.nlm.nih.gov/34365295/

https://www.sciencedirect.com/science/article/pii/S0031942221002065?via%3Dihub

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“α-Pinene Enhances the Anticancer Activity of Natural Killer Cells via ERK/AKT Pathway. Our findings demonstrate that α-pinene activates NK cells and increases NK cell cytotoxicity, suggesting it is a potential compound for cancer immunotherapy.” https://pubmed.ncbi.nlm.nih.gov/33440866/

“α-Pinene inhibits tumor invasion through downregulation of nuclear factor (NF)-κB-regulated matrix metalloproteinase-9 gene expression in MDA-MB-231 human breast cancer cells. These results suggest that α-pinene has a significant effect on the inhibition of tumor invasion and may potentially be developed into an anti-metastatic drug.”   https://applbiolchem.springeropen.com/articles/10.1007/s13765-016-0175-6

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: systematic review

SciELO - Trends in Psychiatry and Psychotherapy“Introduction: Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and leading to increased burden and morbidity. Clinical presentations are pleomorphic, and clinical management often requires combination of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse events of psychotropic drugs reinforce the need for novel therapeutic options.

Aims: To review the evidence supporting the use of medical cannabinoids for the treatment of neuropsychiatric symptoms of dementia (NPS).

Results: Fifteen publications with original clinical data were retrieved, being 5 controlled clinical trials, 3 open-label/observational studies, and 7 case reports. Most studies indicated that the use of medical cannabinoids engendered favorable outcomes for the treatment of neuropsychiatric symptoms related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior and sleep and sexual disinhibition.

Conclusion: Medical cannabinoids represent a promising pharmacological approach for the treatment of NPS, with preliminary evidence of benefit at least in moderate to severe dementia. Controlled trials with longitudinal design and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration and concentrations of active compounds (e.g., CBD/THC ratio) in commercial preparations of medical cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/34374269/

Prosocial Effects of Nonpsychotropic Cannabis sativa in Mice

View details for Cannabis and Cannabinoid Research cover image“Introduction: Cannabis sativa L. (C. sativa) is used since ancient times to produce fabrics, baskets, and cords. Later, different ethnic groups used to burn the leaves and flowers of psychotropic cultivars with high Δ9-tetrahydrocannabinol (D9-THC) levels, during the religious or propitiatory rites to alter the state of consciousness. To date, it is not known whether also nonpsychotropic cultivars of C. sativa were used during these rites, and whether these varieties could have an effect on human behavior.

This study aimed to evaluate the behavioral effects of an extract of nonpsychotropic C. sativa (NP-CS) in mice.

Results: RP-HPLC-UV analysis demonstrated that D9-THC was present in lower concentration with respect to other cannabinoids, like cannabidiol. Furthermore, the GC-MS analysis revealed the presence of several terpenoids. Concerning in vivo studies, chronic treatment with NP-CS did not alter body weight, motility, and anxiety and increased social interaction.

Conclusions: This study highlighted the prosocial effects of NP-CS.”

https://pubmed.ncbi.nlm.nih.gov/34370607/

https://www.liebertpub.com/doi/10.1089/can.2021.0017

Therapeutic Potential of Neoechinulins and Their Derivatives: An Overview of the Molecular Mechanisms Behind Pharmacological Activities

Neuroenergetics, Nutrition and Brain Health | Authors“Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties.

An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on.

The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future.

The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties.

The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus.

Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential.”

https://pubmed.ncbi.nlm.nih.gov/34336908/

“In the future, neoquinolines may be introduced into functional foods or dietary compounds (nutraceuticals) that benefit human health by preventing or treating diseases, or by correcting metabolic disorders, or by preventing the progression or recurrence of a pathological situation.”

https://www.frontiersin.org/articles/10.3389/fnut.2021.664197/full

Cannabinoids for skin diseases and hair regrowth

“The use of cannabis for skin diseases and hair regrowth is at the preliminary stage.

Legalization: Many countries have approved cannabis for medical use; however, four countries Canada, Uruguay, South Africa, and Georgia have legalized it for both medical and recreational purposes.

The endocannabinoid system: The endocannabinoid system may maintain skin homeostasis; two notable endocannabinoids include 2-Arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA).

Routes of administration and pharmacokinetics: Topical cannabinoids can avoid the first-pass metabolism and reduce respiratory side effects; however, the high hydrophobicity of cannabinoids may hinder percutaneous absorption.

Skin disorders and hair growth: Human clinical studies suggest that cannabinoids may be used in eczema, acne, pruritus, and systemic sclerosis treatment. Cannabidiol (CBD) may enhance hair growth via multiple mechanisms.

Safety: Topical cannabis may cause mild side effects such as pruritus, burning, erythema, and stinging; they are relatively safer than inhalation and oral cannabis. Cannabis use may be associated with allergic symptoms and reduced immune response to live vaccination.

Cannabinoids in practice: Despite growing interest, dermatologists should be cautious prescribing cannabinoids due to insufficient clinical data on both efficacy and safety.”

https://pubmed.ncbi.nlm.nih.gov/34363728/

https://onlinelibrary.wiley.com/doi/10.1111/jocd.14352

 

The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation

molecules-logo“Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.”

https://pubmed.ncbi.nlm.nih.gov/34361704/

https://www.mdpi.com/1420-3049/26/15/4551

Myrcene-What Are the Potential Health Benefits of This Flavouring and Aroma Agent?

Neuroenergetics, Nutrition and Brain Health | Authors“Myrcene (β-myrcene) is an abundant monoterpene which occurs as a major constituent in many plant species, including hops and cannabis. It is a popular flavouring and aroma agent (food additive) used in the manufacture of food and beverages. This review aims to report on the occurrence, biological and toxicological profile of β-myrcene. The main reported biological properties of β-myrcene-anxiolytic, antioxidant, anti-ageing, anti-inflammatory, analgesic properties-are discussed, with the mechanisms of activity. Here we also discuss recent data regarding the safety of β-myrcene. Overall, β-myrcene has shown promising health benefits in many animal studies. However, studies conducted in humans is lacking. In the future, there is potential for the formulation and production of non-alcoholic beers, functional foods and drinks, and cannabis extracts (low in THC) rich in β-myrcene.”

https://pubmed.ncbi.nlm.nih.gov/34350208/

“β-Myrcene characteristically gives cannabis strains a mildly sweet flavour profile and provides scent notes that are spicy, earthy and musky. Cannabis strains which contain high concentrations of myrcene (>0.5% myrcene), are likely to induce sedative qualities (“couch-lock effect”), which are classically attributed to Cannabis indica Lam (a synonym of C. sativa L.) strains. On the other hand, strains low in β-myrcene (<0.5%) are likely to induce a more energic “high”.β-Myrcene reported biological activities include analgesic, sedative, antidiabetic, antioxidant, anti-inflammatory, antibacterial, and anticancer effects.”

https://www.frontiersin.org/articles/10.3389/fnut.2021.699666/full

Anti-depressant effects of ethanol extract from Cannabis sativa (hemp) seed in chlorpromazine-induced Drosophila melanogaster depression model

Publication Cover“Context: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. Cannabis sativa L. (Cannabaceae) has long been used to treat pain, nausea, and depression.

Objective: This study investigates the anti-depressant effects of C. sativa (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced Drosophila melanogaster depression model.

Results: The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (p < 0.001) and behavioural factors (p < 0.001). These results correlate with increased transcript levels of dopamine (p < 0.001) and serotonin (p < 0.05) receptors and concentration of dopamine (p < 0.05), levodopa (p < 0.001), 5-HTP (p < 0.05), and serotonin (p < 0.001) compared to those in the control group.

Discussion and conclusions: Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced Drosophila model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.”

https://pubmed.ncbi.nlm.nih.gov/34362287/

“CPZ induces depression-like symptoms, such as changes in behavioural patterns, transcription levels of neurotransmitter receptors, and depression-related neurotransmitter levels in the D. melanogaster depression model. However, administration of HE restores the circadian rhythms, improves locomotor activity, and significantly increases transcription levels of dopamine and serotonin receptors in the depression-induced flies. Based on these findings, we can conclude that HE alleviates depression-like symptoms by increasing the levels of serotonin and dopamine receptors and dopamine, L-DOPA, 5-HTP, and serotonin levels in the brain.”

https://www.tandfonline.com/doi/full/10.1080/13880209.2021.1949356

A pilot safety, tolerability and pharmacokinetic study of an oro-buccal administered cannabidiol-dominant anti-inflammatory formulation in healthy individuals: a randomized placebo-controlled single-blinded study

SpringerLink“Background: The cannabis plant presents a complex biochemical unit of over 500 constituents of which 70 or more molecules have been classified as cannabinoids binding to cannabinoid receptors. The study aimed to investigate the safety, tolerability, and preliminary pharmacokinetics of a nanoparticle CBD formulation.

Results: The study met the primary outcomes of safety, tolerability, and preliminary pharmacokinetics of a standardized CBD-dominant anti-inflammatory extract for oro-buccal administration. Bioavailability of a 6 mg and 18 mg dose of CBD (median IQR) was 0.87 and 8.9 ng h mL-1, respectively. The maximum concentration of CBD for the low and high doses administered once per day occurred at 60 min for both concentrations. The median half-life of the 6 mg and 18 mg CBD dose was 1.23 and 5.45 h, respectively. The apparent clearance of CBD was 115 and 34 L min-1 for a 6 mg and 18 mg dose, respectively.

Conclusion: The oro-buccal nanoparticle formulation achieved plasma concentrations that were largely comparable to other commercial and investigated formulations relative to the concentrations administered. Moreover, there were no reports of adverse effects associated with unfavorable inflammatory sequalae.”

https://pubmed.ncbi.nlm.nih.gov/34357480/

https://link.springer.com/article/10.1007%2Fs10787-021-00859-y

The Effects of Cannabis sativa L. Extract on Oxidative Stress Markers In Vivo

life-logo“In recent decades, a lot of attention has been paid to Cannabis sativa L. due to its useful applications, including in fibers, oil, food for humans and animals, and therapeutics.

The present study aimed to determine antioxidant activity of cannabinoids in Cannabis sativa L. in vivo, evaluating the possible antioxidative effect of Cannabis sativa L. extract (CE) on malondialdehyde (MDA) and glutathione (GSH) concentrations as well as on catalase (CAT) activity in BALB/c mice.

The findings in vivo indicate that Cannabis sativa L. is a good source of natural antioxidants and can be used in the management of oxidative stress.”

https://pubmed.ncbi.nlm.nih.gov/34357019/

https://www.mdpi.com/2075-1729/11/7/647