“Medicinal cannabis” is defined as the use of cannabis-based products for the treatment of an illness. Investigations of cannabis compounds in psychiatric and neurological illnesses primarily focus on the major cannabinoids, cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (Δ⁹-THC), which are hypothesised to benefit multiple illnesses manifesting cognitive impairment, neurodegeneration and neuro-inflammation, as well as chronic pain, epilepsy and post-traumatic stress disorder, respectively. The cannabis plant contains >500 compounds, including terpenes responsible for the flavour and fragrance profiles of plants. Recently, research has begun providing evidence on the potential use of certain plant-derived terpenes in modern medicine, demonstrating anti-oxidant, anti-inflammatory, and neuroprotective effects of these compounds. This review examined the effects of two key terpenes, pinene and linalool, on parameters relevant to neurological and psychiatric disorders, highlighting gaps in the literature and recommendations for future research into terpene therapeutics. Overall, evidence is mostly limited to preclinical studies and well-designed clinical trials are lacking. Nevertheless, existing data suggests that pinene and linalool are relevant candidates for further investigation as novel medicines for illnesses, including stroke, ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (relevant to Alzheimer's disease and ageing), insomnia, anxiety, and depression. Linalool and pinene influence multiple neurotransmitter, inflammatory and neurotrophic signals as well as behaviour, demonstrating psycho-activity (albeit non-intoxicating). Optimising the phytochemical profile of cannabis chemovars to yield therapeutic levels of beneficial terpenes and cannabinoids, such as linalool, pinene and CBD, could present a unique opportunity to discover novel medicines to treat psychiatric and neurological illnesses; however, further research is needed.

Oxidative stress is a common characteristic of psychiatric, neurological, and neurodegenerative disorders. Therefore, compounds that are neuroprotective and reduce oxidative stress may be of interest as novel therapeutics. Phenolic, flavonoid and anthocyanin content, ORAC and DPPH free radical scavenging, and Cu²⁺ and Fe²⁺ chelating capacities were examined in variations (fresh/capsule) of Queen Garnet plum (QGP, Prunus salicina), black pepper (Piper nigrum) clove (Syzygium aromaticum), elderberry (Sambucus nigra), lemon balm (Melissa officinalis) and sage (Salvia officinalis), plus two blends (Astralagus membranaceus—lemon balm-rich, WC and R8). The ability of samples to prevent and treat H₂O₂-induced oxidative stress in SH-SY5Y cells was investigated. Pre-treatment with WC, elderberry, QGP, and clove prevented the oxidative stress-induced reduction in cell viability, demonstrating a neuroprotective effect. Elderberry increased cell viability following oxidative stress induction, demonstrating treatment effects. Clove had the highest phenolic and flavonoid content, DPPH, and Cu²⁺ chelating capacities, whereas QGP and elderberry were highest in anthocyanins. Black pepper had the highest ORAC and Fe²⁺ chelating capacity. These findings demonstrate that plant extracts can prevent and treat oxidative stress-induced apoptosis of neuron-like cells in vitro. Further research into phytochemicals as novel therapeutics for oxidative stress in the brain is needed.

Phytochemicals, including phenolic compounds and terpenes, are of interest for the treatment and prevention of conditions with oxidative stress, inflammatory and neurodegenerative pathologies. Certain plant foods have shown beneficial effects for the brain; however, the specific phenolic and terpene species in these foods are unclear. The present study aimed to characterise and quantify the phenolic, anthocyanidin and terpene species in six plant foods (Queen Garnet plum (QGP, Prunus salicina); black pepper (BPF, Piper nigrum); clove (CF, Syzygium aromaticum); elderberry (EF, Sambucus nigra); lemon balm (LBF, Melissa officinalis); and sage (SF, Salvia officinalis)) and six plant food-based complementary products (clove (CC), elderberry (EC), lemon balm (LBC), and sage (SC), plus two blends (Astragalus membranaceus and lemon balm-rich, WC and R8)). The relationships between the concentration of phytochemical species in these samples and their antioxidant capacities (i.e. oxygen and nitrogen free radical scavenging, Cu²⁺ and Fe²⁺ chelating capacities, and the ability to prevent H₂O₂-induced oxidative stress in neuroblast-like SH-SY5Y cells, in vitro) were also examined. WC had the highest concentration of phenolics, followed by QGP, EF, CC and CF. BPF had the highest total terpene concentration followed by CC, CF and SF. Correlations between certain compounds and antioxidant capacity were demonstrated. The results provide insight into the potential functional capabilities of species of phenolics and terpenes. Understanding the phytochemical profile of plant foods and their correlations may be important in understanding their potential therapeutic benefits for brain health.

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.