Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression.

Behavioural Brain Research“Chronic stress is depressogenic by altering neurotrophic and neuroinflammatory environments of the organism. The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with endocannabinoid receptors. β-Caryophyllene (BCP) is a CB2 agonist that exhibited anti-inflammatory, analgesic effects but minimal psychoactive effects. To test if BCP exhibits antidepressant-like action, animals were chronically restrained with additional stressors for 28 days, and BCP (25, 50, 100 mg/kg) was intraperitoneally injected once a day during the stress inflicting period. Then despair related behaviors and hippocampal expression of neurotrophic, inflammatory and cannabinoid receptor levels were measured. To test the effect of BCP on long-term depression, field potentials were measured during the application of lipopolysaccharide and low frequency stimulation. In the tail suspension test and forced swim test, chronic stress-induced despair behaviors were reduced by BCP. Also BCP improved the stress-related changes in the hippocampal expression of COX-2, BDNF, and CB2 receptor expression. In organotypic hippocampal slices, BCP reduced the lipopolysaccharide-induced intensification of the long-term depression. In conclusion, BCP improved chronic stress related behavioral and biochemical changes. These results suggest that BCP may be effective in treating depression and stress related mental illnesses.”

https://www.ncbi.nlm.nih.gov/pubmed/31862467

https://linkinghub.elsevier.com/retrieve/pii/S0166432819313348

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”    https://www.ncbi.nlm.nih.gov/pubmed/18574142

Influence of the CB1 and CB2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice.

Pharmacology Biochemistry and Behavior“Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders.

Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine.

In summary, the outcomes of the present study showed that activation and inhibition of CB1 receptors as well as inhibition of CB2 receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB1 and CB2 receptors has a potential to augment the antidepressant activity of agomelatine.”

https://www.ncbi.nlm.nih.gov/pubmed/31785246

https://www.sciencedirect.com/science/article/pii/S0091305719304873?via%3Dihub

Antidepressant active ingredients from herbs and nutraceuticals used in TCM: pharmacological mechanisms and prospects for drug discovery.

Pharmacological Research“Depression is a widespread psychological disorder that affects up to 20% of the world’s population. Traditional Chinese medicine (TCM), with its unique curative effect in depression treatment, is gaining increasing attention as the discovery of novel antidepressant drug has become the pursuit of pharmaceutical. This article summarizes the work done on the natural products from TCM that have been reported to conceive antidepressant effects in the past two decades, which can be classified according to various mechanisms including increasing synaptic concentrations of monoamines, alleviating the hypothalamic-pituitary-adrenal (HPA) axis dysfunctions, lightening the impairment of neuroplasticity, fighting towards immune and inflammatory dysregulation. The antidepressant active ingredients identified can be generally divided into saponins, flavonoids, alkaloids, polysaccharides and others. Albiflorin, Baicalein, Berberine chloride, beta-Asarone, cannabidiol, Curcumin, Daidzein, Echinocystic acid (EA), Emodin, Ferulic acid, Gastrodin, Genistein, Ginsenoside Rb1, Ginsenoside Rg1, Ginsenoside Rg3, Hederagenin, Hesperidin, Honokiol, Hyperoside, Icariin, Isoliquiritin, Kaempferol, Liquiritin, L-theanine, Magnolol, Paeoniflorin, Piperine, Proanthocyanidin, Puerarin, Quercetin, Resveratrol (trans), Rosmarinic acid, Saikosaponin A, Senegenin, Tetrahydroxystilbene glucoside and Vanillic acid are Specified in this review. Simultaneously, chemical structures of the active ingredients with antidepressant activities are listed and their sources, models, efficacy and mechanisms are described. Chinese compound prescription and extracts that exert antidepressant effects are also introduced, which may serve as a source of inspiration for further development. In the view of present study, the antidepressant effect of certain TCMs are affirmative and encouraging. However, there are a lot of work needs to be done to evaluate the exact therapeutic effects and mechanisms of those active ingredients, specifically, to establish a unified standard for diagnosis and evaluation of curative effect.”

https://www.ncbi.nlm.nih.gov/pubmed/31706012

https://www.sciencedirect.com/science/article/abs/pii/S1043661819322601?via%3Dihub

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice.

Behavioural Brain Research“Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the CB receptors may affect the activity of the frequently prescribed antidepressant drugs.

Our interests have been particularly focused on the potential influence of the CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 – CB2 receptor agonist and AM630 – CB2 receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine).

Summarizing, the results of the present study revealed that both activation and inhibition of the CB2 receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background.”

https://www.ncbi.nlm.nih.gov/pubmed/31626848

“Interplay between CB2 receptor ligands and antidepressants is pharmacodynamic in nature.”

https://www.sciencedirect.com/science/article/pii/S0166432819311891?via%3Dihub

Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model.

Environmental Toxicology and Pharmacology

“Cannabidiol (CBD) exhibits significant efficacy in mental and inflammatory diseases. Several studies have recently reported on the rapid antidepressant-like effects of CBD, suggesting that CBD is a potential anti-depressant or anti-stress drug. However, CBD is mainly administered orally or by inhalation with poor bioavailability, resulting in high costs. We aim to explore the efficacy of long-term periodic administration of CBD in chronic mild stress (CMS) via two routes and its pharmacokinetics. We treated ICR mice with CBD administered orally and intravenously and then determined the kinetic constants. A single bolus intravenous injection of CBD resulted in a half-life of 3.9 h, mean residence time of 3.3 h, and oral bioavailability of about 8.6%. The antidepressant-like effects of periodically administered CBD on the chronic mild stress mouse model are evaluated. Results demonstrated that such treatment at a high dose of 100 mg/kg CBD (p.o.) or a low dose of 10 mg/kg CBD (i.v.), elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus. Our findings are expected to provide a reference for the development of intravenous antidepressant formulations of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31173966

https://www.sciencedirect.com/science/article/pii/S1382668919300687?via%3Dihub

Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors.

Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Long-term single housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic, antidepressant, and antipsychotic drugs.

Preclinical and clinical findings indicate that cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, has anxiolytic, antidepressant, and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behaviors.

Here, we investigated whether CBD (5, 15, 30, and 60 mg/kg; i.p.) could attenuate social isolation-induced aggressive behavior in the resident-intruder test.

Taken together, our findings suggest that CBD may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31054943

https://www.sciencedirect.com/science/article/pii/S0278584618308340?via%3Dihub

cannabidiol reduces aggressiveness, study concludes”  https://globalhealthnewswire.com/2019/07/31/cannabidiol-reduces-aggressiveness-study-concludes/

Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms.

Journal of Chemical Neuroanatomy

“Significant limitations with the currently available antidepressant treatment strategies have inspired research on finding new and more efficient drugs to treat depression. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa, and emerges in this regard as a promising compound. In 2010, we were the first laboratory to demonstrate that CBD is effective in animal models of predictive of antidepressant effect, a finding now confirmed by several other groups. Recent evidence suggests that CBD promotes both a rapid and a sustained antidepressant effect in animal models. CBD has a complex pharmacology, with the ability to interact with multiple neurotransmitter systems involved in depression, including the serotonergic, glutamatergic, and endocannabinoid systems. Moreover, CBD induces cellular and molecular changes in brain regions related to depression neurobiology, such as increased Brain Derived Neurotrophic Factor (BDNF) levels and synaptogenesis in the medial prefrontal cortex, as well as it increases neurogenesis in the hippocampus. This review presents a comprehensive critical overview of the current literature related to the antidepressant effects of CBD, with focus at the possible mechanisms. Finally, challenges and perspectives for future research are discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/31039391

https://www.sciencedirect.com/science/article/pii/S0891061818302114?via%3Dihub

Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.

molecules-logo

“Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/31013866

https://www.mdpi.com/1420-3049/24/8/1459

Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.

Biomedicine & Pharmacotherapy

“The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses.

It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30970516

https://www.sciencedirect.com/science/article/pii/S0753332218375309?via%3Dihub

“Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

β-Caryophyllene, a Natural Sesquiterpene, Attenuates Neuropathic Pain and Depressive-Like Behavior in Experimental Diabetic Mice.

 View details for Journal of Medicinal Food cover image“Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required.

β-caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders. For this reason, we assessed whether BCP modulates nociception, anxiety, and depressive-like behavior in streptozotocin (STZ)-induced experimental diabetic BALB/c female mice.

BCP was orally chronic administrated (10 mg/kg/60 μL). Pain developed with STZ was evaluated with von Frey filament test, SMALGO®, and hot plate test. Anxiety and depression-like behavior were assessed by marbles test, forced swim test, and tail suspension test. BCP significantly reduced glycemia in experimental diabetic mice. The pain was also mitigated by BCP administration. Depression-like behavior assessed with tail suspension test was attenuated with orally chronic BCP administration. Substance P and cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were also attenuated with BCP administration. NP was positively correlated with substance P and IL-6 and IL-1β release.

Our data using an orally chronic BCP administration in the STZ challenged mice to suggest that glycemia, diabetes-related NP, and depressive-like behavior could be prevented/reduced by dietary BCP.”

https://www.ncbi.nlm.nih.gov/pubmed/30864870

https://www.liebertpub.com/doi/10.1089/jmf.2018.0157

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142