David O. Kennedy, professor of Biological Psychology and the director of the Brain, Performance and Nutrition Research Centre at Northumbria University in the UK, has written a most thought-provoking book that provides us with a detailed explanation of the relationship between humans and plants.

Kennedy not only provides us with the complex biochemistry of the plant compounds which have such a significant influence on our cognitive performance and emotional wellbeing, but also outlines the history and traditional uses of plants within many ancient and traditional cultures. I was fascinated with the evolutionary relationship of plants and animals and now have a much better understanding of why so many plant-based chemicals can have such a profound psychological influence.

In his first chapter, From Shamans to Starbucks, he explains how many shamanic traditions throughout every corner of the globe made use of psychotropic plants to enhance their spiritual experience. He explains that the common feature underlying the relationship between these natural psychotropics and religions throughout the world is that they were always used to provoke an altered state of consciousness, either a trance or a hallucinatory state that served as a gateway to a spiritual or religious experience and/or communication with the spirits.

Research now shows that entheogens such as the hallucinogen psilocybin (the principal active chemical in Psilocybe mushrooms) consistently promote altered states of consciousness that are described by consumers as mystical or spiritual. Kennedy points out that this effect occurs irrespective of the nature of the consumer’s religious or spiritual beliefs or as he says, lack of belief.

He asks the question: So, where have all the shamans gone? He claims that the rise of monotheistic religions was responsible for suppressing the use of psychoactive plants. He suggests that it was Christianity with the inquisitions and the witch hunts that raged through Europe in the 13th century through to the 17th century that supressed the use of entheogenic plants. The term entheogenic originates from the Greek “entheos” meaning “god within”, relating to any psychoactive substance used to engender a spiritual experience.

Kennedy provides us with a very good explanation of the co-evolution of plants, insects and humans. He explains that the fundamental internal cellular signaling pathways were established some 1.6 billion years ago when plants and animals diverged. These pathways, he claims, have been strongly conserved, and to this day the same genes and chemicals are used between plants and animals.

We should be familiar with the term secondary metabolites – essential oils are referred to as secondary metabolites. Kennedy explains that as phytochemicals they do not play a direct role in the ‘primary’ metabolic processes that underpin the plant’s survival, growth, development or reproduction. However, they do play a wide range of general and protective roles as antioxidant, free-radical scavenging, ultraviolet light-absorbing and antiproliferative agents, and they defend the plant against microorganisms such as bacteria, viruses and fungi. They also manage interplant relationships and act as allelopathic defenders of the plant’s growing space against competitor plants. Secondary metabolites have a more complex role in dictating or modifying the plant’s relationship with other complex organisms. The most obvious role is the attraction of pollinators or the provision of indirect defenses for the plant by attracting the natural enemies of their herbivorous attackers. He states that more than 70% of all plant species are entirely reliant on symbiotic insect interaction for pollination.

A diverse range of plant secondary metabolites are able to modulate the functioning of the human brain. Most of these secondary metabolites fall into three chemical groups: the phenolics, the terpenes, and the alkaloids. I was particularly interested in the chapter on terpenes, as these are the most common constituents found in essential oils.

He explains that many of the neurotransmitters, neuromodulators and hormones that are integral to the functioning of our own nervous system are in fact the chemical products of metabolic processes that existed before the differentiation of plants and animals over a billion years ago. Many of these neurochemicals play key roles in the lives of plants, often sharing functional similarities with the roles they play as signalling molecules in mammals.

For example, the key neurotransmitter acetylcholine (which I will talk about in another blog that will examine the role of essential oils for dementia) plays an important role in the functioning of the parasympathetic nervous system and contributes to the majority of the brain processes including neural plasticity, sensory perception, arousal and attention. In plants, acetylcholine contributes to the regulation of growth, germination, flowering, water homoeostasis and photosynthesis.

He explains that the insect and mammalian nervous system make use of the same neurochemicals, including neuropeptides, hormones and neurotransmitters and their associated receptors.

Kennedy asks the question: Why do plant secondary metabolites affect human brain function?

He proposes two hypotheses. The first is that secondary metabolites modify human brain function because plants and humans share diverse cellular, biochemical and molecular similarities. The second is that they modify human brain function because insects and humans share strikingly similar nervous systems.

I was so excited that Kennedy dedicated an entire chapter to the Lamiaceae plant family. It is the sixth largest family of angiosperms, comprising of 236 genera and 7,200 species of plants. He was particularly interested in the Salvia genus and the smaller genera Melissa and Rosmarinus. He explains that all these genera have psychotropic species.

For example, Salvia officinalis and S. lavandulaefolia are often indicated for the attenuation of poor memory, mental confusion, depression and vertigo. Both varieties of sage contain about 1.0% to 2.8% essential oil which is mainly composed of α-pinene, β-pinene, 1,8-cineole, camphor, geraniol, borneol and camphene. The oil also contains sesquiterpenes such as α-humulene and β-caryophyllene. The only major difference is that S. lavandulaefolia lacks the α-thujone and β-thujone found in S. officinalis. Kennedy explains that both these ketones are considered to be toxic convulsants; however, it should be noted that S. officinalis does not exhibit the toxicity in humans that its thujone content might suggest.

He states that a number of terpene compounds such as borneol bind allosterically to inhibitory ionotropic GABA receptors and that the essential oils and alcoholic extracts of both sage plants have been identified as inhibiting acetylcholinesterase (AChE) in in vitro and in vivo studies. He reports that the cholinesterase-inhibiting properties have also been shown to be due to synergistic and antagonistic interactions between various terpene compounds. For example, 1,8-cineole works synergistically with α-pinene and caryophyllene, but antagonistically with camphor.

Kennedy cites many studies demonstrating the cholinergic activities of S. officinalis and S. lavandulaefolia. A double-blind placebo-controlled, balanced crossover study in healthy young humans demonstrated memory improvements within 1 hour and 2.5 hours of taking a single oral dose of 50 µl and 100 µl of S. lavandulaefolia essential oil. He also cites that similar mnemonic effects were subsequently confirmed after single doses of 25 µL and 50 µL of the same essential oil, as well as improved performance on a mental arithmetic task and improved levels of subjective alertness, calmness and contentment. In another study, the treatment with an encapsulated essential oil of S. lavandulaefolia was found to have a very potent acetylcholinesterase inhibitory activity.

Kennedy points out that while the cholinergic properties underlie the cognitive enhancement of sage extracts, it needs to be noted that sage extracts also exert antioxidant, anti-inflammatory and mildly oestrogenic properties, all of which are important to improve brain function, both in healthy populations and sufferers from age-associated cognitive decline and dementia. He explains that sage extracts are well tolerated and exhibit fewer unwanted side effects at levels likely to be consumed by humans, making them a potential replacement for the side-effect-prone, alkaloid-based cholinesterase inhibitors that are typically prescribed for the attenuation of the cognitive deficits related to Alzheimer’s disease.

Kennedy cites many in vitro studies involving Melissa officinalis extracts that confirm psychotropic activity including antioxidant properties, direct nicotinic and muscarinic cholinergic receptor-binding properties in human brain tissue and AChE inhibitory properties. He cites three double-blind, placebo-controlled studies that assessed the effects of melissa in dementia patients. The results found improvements in agitation and quality of life following aromatherapy treatment with melissa in 71 patients with severe dementia.

Kennedy suggests that the cognitive-enhancing effects of rosemary may relate to the interactions with the cholinergic system. One study using the fresh leaf and essential oil of rosemary demonstrated significant in vitro cholinergic receptor-binding and AChE-inhibiting properties in human brain tissue. The AChE-inhibitory activity has been confirmed in vivo in mice following oral administration.

Kennedy is cynical that mainstream medicine and the pharmaceutical industry is not likely to be interested in complex plant mixtures that have poorly understood synergistic and polyvalent activities. He explains that they prefer mono-treatments with a well-characterised mode of action. He gives us an example with Alzheimer’s disease:

The sad case of Alzheimer’s disease illustrates this nicely. Currently, the first-line treatments offered to attenuate the cruel cognitive declines seen in dementia are a handful of cholinesterase inhibitors, including the plant-derived alkaloid rivastigmine and galantamine. Alkaloids are toxic by their very nature, and in the case of these treatments they have limited efficacy that has to be carefully balanced with their high level of cholinergic side effects.

He suggests that the terpene-rich extracts of the Salvia species have demonstrated synergistic cholinesterase inhibitory and other polyvalent effects on a number of other potentially beneficial parameters. They are also significantly safer for human consumption with no significant side effects and would be much more cost-effective in providing an effective treatment for the cognitive symptoms of Alzheimer’s disease. However, he laments that we have a poor understanding of the many interactions within complex plant-derived extracts and that there is still to, a large extent, generally poor-quality evidence surrounding the efficacy of many herbal extracts.

I love his concluding statement. This is always something that I have argued and stated:

Answering the simple question of why plant chemicals modulate brain function requires the integration of thoughts and concepts from a diverse range of disciplines including molecular biology and biochemistry, plant science, zoology, entomology, pharmacology, medicine, neuroscience and psychology. The necessary dismantling of discipline “silos” may have some interesting emergent, synergistic properties that go beyond answering this simple question.

This is an important book which I believe will open the doors to a new understanding of the important role of many essential oils. I give Plants and the Human Brain five stars!

Plants and the Human Brain
By David O. Kennedy
Published by Oxford University Press, 2014.