“Persistent low mood, anxiety and cognitive deficits are common symptoms of depression and highly efficacious treatments that address symptoms including cognitive dysfunction are still required.

β-caryophyllene (BCP) is a terpene with anti-inflammatory and pro-cognitive properties; however, its efficacy on cognition in depression remains unclear.

This study aimed to investigate acute and chronic BCP treatment effects on cognitive, depressive- and anxiety-like behaviours, and inflammation in male and female Wistar-Kyoto (WKY) rats, a rodent model of treatment-resistant depression.

Rats were administered either BCP (50 mg/kg) or vehicle (control). Open field (OFT), social interaction, sucrose preference, novel object recognition (NOR) and elevated plus maze (EPM) tests were conducted after acute (1 h) and chronic (2 weeks) treatment. Peripheral plasma inflammatory cytokine levels were examined.

BCP acutely increased locomotor activity in the OFT but did not improve social interaction, whereas chronic BCP prevented increased latency to first interaction in females (not males). BCP did not improve sucrose preference or prevent anxiety-like behaviours in the EPM. BCP significantly increased novel object discrimination in the NOR test in male and female WKY rats and reduced cytokine levels after chronic treatment.

This study shows for the first time that chronic BCP treatment improved recognition memory and exerted anti-inflammatory properties in a rodent model of depressive-like behaviours. BCP did not significantly improve anxiety-like behaviours, social interaction or anhedonia in WKY rats of either sex.

These findings demonstrate the pro-cognitive effects of BCP in a rodent model of treatment-resistant depression worthy of further investigation.”

https://pubmed.ncbi.nlm.nih.gov/40049345/

https://www.sciencedirect.com/science/article/pii/S0278584625000661?via%3Dihub

“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

“Evidence indicates a bidirectional link between depressive symptoms and neuroinflammation. This study evaluated chronic cannabidiol (CBD) treatment effects in male and female rats subjected to the unpredictable chronic mild stress (UCMS) model of depression.

We analyzed the gene expression related to neuroinflammation, cannabinoid signaling, estrogen receptors, and specific microRNAs in the ventromedial prefrontal cortex (vmPFC), CA1, and ventral subiculum (VS). UCMS influenced immobility in a sex-specific manner, increasing it in males and decreasing it in females, effects that were reversed by CBD.

CBD also normalized the UCMS-induced upregulation of tumor necrosis factor α (TNF-α) in the CA1 and VS in males. In both sexes, UCMS induced the upregulation of the nuclear factor kappa B subunit 1 (NF-κB1) gene in the VS, which was unaffected by CBD. Additionally, CBD reversed CB1 downregulation in the VS of males but not in the vmPFC of either sex. In males, CBD restored the UCMS-induced downregulation of VS estrogen receptor genes ERα and ERβ. UCMS also altered miR-146a-5p expression, downregulating it in females (VS) and upregulating it in males (CA1), with no CBD effect.

These findings highlight the sex-specific mechanisms of CBD’s antidepressant effect, with hippocampal neuroinflammatory and estrogenic pathways playing a key role in males.”

https://pubmed.ncbi.nlm.nih.gov/39851527/

“Cannabidiol (CBD), renowned for its anti-inflammatory and antioxidative properties, has emerged as a promising candidate for treating depression.”

https://www.mdpi.com/2073-4409/14/2/99

“Cannabidiol (CBD), a non-psychotropic compound derived from Cannabis sativa, is known for its potential therapeutic effects on central nervous system (CNS) disorders.

This study investigates the effects of chronic CBD administration on depressive and cognitive alterations induced by social isolation in male C57BL/6 mice. The experimental design involved adult mice subjected to either group housing or 12 weeks of social isolation. Behavioral assessments, including the sucrose preference test, open field test, light/dark box, novel object recognition, and tail suspension test, were performed to evaluate the impact of CBD on emotional and cognitive alterations. Additionally, hippocampal gene expression for cannabinoid type 1 receptors (CB1R), serotonin type 1A receptors (5HT1AR), and brain-derived neurotrophic factor (BDNF) were analyzed.

Results indicate that CBD mitigated anhedonia in isolated mice and reduced immobility episodes in the TST. However, CBD did not exert significant anxiolytic effects and unexpectedly induced anxiety-like behavior in group-housed mice. The study also revealed that social isolation impaired recognition memory and reduced BDNF expression, while CBD treatment protected memory in isolated mice.

These findings suggest that CBD has potential antidepressant and neuroprotective effects in social isolation-induced depressive models, although its anxiogenic effects in non-stressed mice warrant further investigation.”

https://pubmed.ncbi.nlm.nih.gov/39725273/

“Cannabidiol (CBD) is a non-psychotropic, lipophilic phytocannabinoid of Cannabis sativa plants. CBD has been reported as a potential therapeutic agent for central nervous system (CNS) disorders due to its high permeability across the blood-brain barrier and its pleiotropic neuropharmacological effects “

“The results of this study demonstrate that chronic CBD administration attenuates depressive-like behaviors and protects cognitive function in SI male mice. Specifically, CBD mitigated anhedonia, a hallmark of depression, and reduced immobility in the TST, indicating an antidepressant-like effect.”

https://www.sciencedirect.com/science/article/abs/pii/S0166432824005643?via%3Dihub

“Background: Depression is a prevalent and disabling disorder that poses serious problems in mental health care, and rapid antidepressants are novel treatments for this disorder. Cannabidiol (CBD), a non-intoxicating phytocannabinoid, is thought to have therapeutic potential due to its important neurological and anti-inflammatory properties. Despite major advances in pharmacotherapy in experimental animals, the exact mechanism of antidepressant-like effects remains to be elucidated.

Methods: In this paper, we review the current state of knowledge on the antidepressant properties of CBD in numerous experimental and clinical studies.

Results: Accumulating evidence suggests that CBD has antidepressant properties in humans and animals with few side effects, suggesting that CBD may be a potential antidepressant. Furthermore, we discuss CBD may therefore provide a potential treatment to exert antidepressant-like effects through various molecular targets, reducing inflammation, and enhancing neurogenesis.

Conclusions: Taken together with the growing popularity of CBD as a medicine, these findings extend the limited knowledge on the antidepressant effects of CBD. This potentially opens up new therapeutic means for the patients with depression.”

https://pubmed.ncbi.nlm.nih.gov/39657242/

https://academic.oup.com/ijnp/advance-article/doi/10.1093/ijnp/pyae064/7918373?login=false

“Background: Lipopolysaccharide (LPS)-induced neuroinflammation is a well-established model for studying depression-like behavior, driven by pro-inflammatory cytokines such as TNF-α and IL-1β. Mast cells (MCs) contribute to neuroinflammation by releasing mediators that exacerbate depressive-like symptoms. This study evaluates the antidepressant-like and anti-inflammatory effects of Cannabis sativa L. inflorescence extract (CSL) in an LPS-induced neuroinflammation model.

Methods: Male C57BL/6 mice were intraperitoneally injected with CSL at doses of 10, 20, and 30 mg/kg, 30 min prior to LPS (0.83 mg/kg) administration. Depressive behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). The neutrophil-to-lymphocyte ratio (NLR) was measured to assess systemic inflammation. Cytokine levels in the prefrontal cortex (PFC) were measured, and mast cell degranulation in the lymph nodes and dura mater was analyzed histologically (approval number: WKU24-64).

Results: CSL significantly improved depressive-like behaviors and decreased the NLR, indicating reduced systemic inflammation. CSL also significantly reduced TNF-α and IL-1β levels in the PFC. Furthermore, CSL inhibited MC degranulation in the deep cervical lymph nodes and dura mater, with the strongest effects observed at 30 mg/kg.

Conclusions: CSL demonstrated antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammation model, likely through the modulation of cytokine expression and mast cell activity. These results suggest the potential of CSL as a therapeutic option for treating inflammation-related depression.”

https://pubmed.ncbi.nlm.nih.gov/39459047/

“We demonstrated that CSL exhibits significant antidepressant-like and anti-inflammatory effects in an LPS-induced neuroinflammatory model. CSL administration effectively reduced depressive-like behaviors, as observed in the SPT, TST, and FST, and modulated the degranulation of MCs in LNs and the dura mater. Furthermore, CSL decreased the expression of pro-inflammatory cytokines TNF-α and IL-1β in the PFC in a dose-dependent manner. These findings suggest that CSL acts both through immune modulation and neuroinflammation suppression, possibly via the endocannabinoid system and pathways such as NF-κB, PPAR-γ, and VEGF-C. The synergistic interaction between cannabinoids and terpenes in CSL likely contributes to its therapeutic potential, supporting the notion of the “entourage effect”. While these results are promising, further studies are required to clarify the exact mechanisms involved and to assess the long-term safety and efficacy of CSL in chronic depression models.”

https://www.mdpi.com/1424-8247/17/10/1409