D-limonene is considered to have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.

https://pubmed.ncbi.nlm.nih.gov/18072821

https://www.healthline.com/nutrition/d-limonene#safety-and-side-effects

Due to its unique ability to bind with CB2 receptors, Beta-caryophyllene has potent anti-inflammatory, antimicrobial, antibacterial, and antioxidant properties. It is known to help relieve anxiety and pain, reduce cholesterol, prevent Osteoporosis, and treat seizures BCP was found to elicit a full agonist action on cannabinoid type 2 (CB2) receptors, a G-protein coupled receptor representing important therapeutic target in several diseases. Activation of CB2 receptors notably appeared devoid of psychotropic adverse effect of cannabinoids contrary to the CB1 receptors. In addition, it activates peroxisome proliferated activator receptors (PPARs) isoforms; PPAR-α &-γ and inhibits pathways triggered by the activation of toll like receptor complex; CD14/TLR4/MD2, reduce immuneinflammatory processes and exhibit synergy with µ-opioid receptor dependent pathways. Additionally, it found as potent antagonist of homomeric nicotinic acetylcholine receptors (α7-nAChRs) and devoid of effects mediated by serotonergic and GABAergic receptors. It also modulates numerous molecular targets by altering their gene expression, signaling pathways or through direct interaction. Various pharmacological activities such as cardioprotective, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antioxidant, anti-inflammatory, antimicrobial and immune-modulator have been reported in experimental studies. It has shown potent therapeutic promise in neuropathic pain, neurodegenerative and metabolic diseases.

Can be a novel candidate for various pathologies considering the polypharmacological and multifaceted therapeutic properties potential along with favorable oral bioavailability, lipophilicity and physicochemical properties.

https://pubmed.ncbi.nlm.nih.gov/26965491/