Biosphere

From genetic analysis, to phytochemical screening, anthropological fieldwork, and bioprospecting this section highlights the true interdisciplinary nature of ethnopharmacology. The discipline has evolved considerably since the first symposium and this section demonstrates aspects of biomedical and chemistry research. It also highlights why this research is more important than ever in a 21st century world.

I: Phylogenetic analysis of traditional medicinal plants: Discovering new drug sources from patterns of cultural convergence

An omnipresent question in my mind is how did people, so long ago, know which plants to use for what? Before modern science and even before a deep anatomical understanding of the body, people understood which plants would heal them and precisely how to use them. What is even more intriguing is that similar plants (and uses) were used in geographically isolated areas, though the cultures had seemingly not coincided.

Phylogenetic ethnopharmacology offers a new perspective on drug discovery. In essence it allows scientists to make predictions about unstudied taxa and helps prioritize what plants should be investigated. This gives guidelines for novel drug discovery from plants, as previously thousands have been randomly scanned which led to very few drug leads.

This essay discusses a few studies one of which was conducted to see if there were genetic similarities between medicinal plants used in different cultures. Another was conducted to group psychoactive plants based on their phylogeny. New York was chosen for its cultural diversity, as the population therefore has a vast array of medicinal plant use. The results showed that different cultural groups through years of trial and error had independently discovered plants with similar bioactivity.

In the New York study plants used by Native Americans, African, Australian and European communities were investigated. Plant groups with the highest relative medicinal importance, in ascending order, include Lamiaceae (used for gastrointestinal and respiratory ailments, represented at c. 5%), Zingiberaceae (8%, gastrointestinal including plants like ginger), Lauraceae (9%, gastrointestinal/antibiotic including plants like cinammon), Meliaceae (10%, antibiotic), Dipsacales (16%, nervous system applications), Fagales (20%, gastrointestinal/antibiotic), and Burseraceae (27%, musculoskeletal ailments). These were some of the most commonly used, culturally overlapping, medicinal plant families found in New York.

II: Ethnopharmacology meets the receptorome: Bioprospecting the psychotherapeutic medicines in the amazon rainforest

In recent years the amount of people recognizing the potential for Amazonian plant medicines has increased rapidly. This is largely due to the infamous plant ayahuasca, with places like Peru becoming a hotspot for "drug tourism". However much less attention has been focused on the other plant medicines from one of the most biodiverse areas on the planet. This study was conducted to identify Amazonian ethnomedicines for potential use of cognitive deficits in schizophrenia and dementia. The basis of many modern drugs for the central nervous system (CNS) are inextricably linked with ethnopharmacology, as humans have shown considerable ingenuity with identifying and using psychotropic plants. A historical example of this is the alkaloid resperine from Rauvolfia serpentine which is traditionally in Ayurveda for treating psychosis. This provided a prototype of modern antipsychotics, and is just one example where psychiatric drugs are explored in modern day ethnopharmacology. It was the hopes of this study that plants in the Amazon could provide such leads.

A method using radioligand receptor-binding (a method to show which receptors a drug binds to) was used on cells in the CNS during this study. This method has been crucial for development in drug discovery as it allows for the labelling of specific receptors, enzymes and other cellular targets. It also allows for rapid screening of compound libraries or extracts made from natural sources.

Plants were chosen based on literature reviews, databases, surveys, herbarium collections and field interviews with traditional healers. A broad set of inclusion criteria was established as there is a lack of uniform terminology and perceptions of mental health between Western scientists and Amazonian traditional healers. Therefore, criteria had to be wide to include all possible candidate plants for investigation.

Overall 228 crude extracts were screened with 91 successful plants that caused >60% inhibition of the radioactive ligand. The largest number of "hits" were in plants that contained indole alkaloids, and after this it was the plants that stimulated 1 or more 5HT receptors meaning X. Other frequently affected receptors included α-adrenergic receptors, opiate receptors, histamine H2 receptors and serotonin receptors. Combining receptor binding assays with ethnopharmacology is a powerful and efficient way to discover and evaluate new psychotropic ethnomedicines which could then go on to be clinically developed.

This study was the first to apply receptor assays to a large number of extracts and fractions from the Amazon. It is still a work in progress, and the results show the benefits and limitations of such methods. It has helped us understand the CNS activity of a subset of Amazonian flora. The scientists also identified relevant plants for future investigation in the hopes that the Amazon and indigenous knowledge can be key resources for the future of the human mind.

III: A preliminary report on two novel psychoactive medicines from northern mozambique

The Lomwe people are believed to have originated from the Congo basin about a thousand years ago, and are still strongly animist today. Many believe they originated from a cave on the sacred Mount Namuli where they believe all people and animals were born. There is said to be a female foot imprinted in the cave which is why there is a matriarchal family structure today.

They live on Mount Mabu which is a relatively rare type of wet forest that has been in isolation for long periods of evolution. Making it today possibly the largest tract of untouched forest in Southern Africa that's at medium altitude. It has high levels of endemic species, but due to the political unrest of in the country, it has been largely untouched by scientists and explorers.

However, in 2017 a preliminary study was conducted over nine days on Mount Mabu to determine medicinal plant uses by healers in a particular community. It consisted of six formal interviews, where it was understood that around 25% of plants were used in conjunction with a ritual or belief system. The researcher was also taken on walks and shown where which plants were used and how.

There was a particular plant healer who was a male in his 40s. In his twenties he began developing what would be known in the West as schizophrenia. Experiencing hearing voices and having visions he was unable to face his community and sought refuge in the forest. Here his deceased grandfather appeared to him in a vision and showed him medicinal plants, which were from then on used for his people. Though extraordinary, it is not a rare phenomenon in Africa for people receive healing wisdom from their ancestors.

This healer described two plants for psychoactive use. The first being Myrothamnus flabellifolius also known as the "resurrection plant", or locally is known as Thriabe. The young leaves are smoked by people for asthma and other chest complaints. It has also been reported that this has a sedative effect similar to cannabis. The second plant is Aeschynomene cristata, known as Mwecheche and it has been shown to be antimicrobial and hepatoprotective. The root bark is scraped, dried, powdered, and sniffed. It causes a change in visual and colour perception, and it is stated that "one can see anything according to his own spirit." pg 315 This medicine was not administered to people unless they asked for it, and it was only really used to "receive answers". It is still revered today as a powerful spiritual tool. Interestingly, participants were also noted giving the plant to their dogs before hunting in order to increase their sensory perception. There is still limited research in this area of Mozambique, but it shows interesting discoveries that indigenous people have made about how to use plants.

IV: Ethnopharmacology: From Mexican hallucinogens to a global transdisciplinary science

This essay covers what ethnopharmacology is, some insight into early and recent research. The definitions of ethnopharmacology discussed in this piece are as follows: "Ethnopharmacology constitutes a respectful marriage between modern science and ancient wisdom with much to be gained in both directions" pg 317, is one of the most eloquent descriptions of ethnopharmacology to date, by Graham Jones who is an ethnopharmacologist. A biomedical definition is, "a science dealing with the study of the pharmacology of traditional medicine and focusing on the active substances and their pharmacological action." pg 317 A more sociocultural description is ,"Ethnopharmacology is the study of the way people use plants, informing us about the varying ways people create meaning about these living objects." pg 317 Among these it is clear that today ethnopharmacology is an open-minded, interdisciplinary science examining humans and plants.

Ethnopharmacology is not a restrictive and rigid field of research, and it is heavily influenced by the academic, political and cultural background of a researcher. It is variable, and thus a unique science. To begin with ethnopharmacology focuses mainly on studying the traditional use of psychoactive substances, however the trajectory of this discipline and the questions it asks has expanded massively. Its popularity continues to rise, as people begin to accept the importance of indigenous knowledge in sculpting a healthy future for the planet and humans. Afterall, I believe indigenous people understand the land in ways most city-dwellers will likely never be able to, and never has knowledge of nature been more vital.

Whilst research of traditional plants dates back hundreds of years, ethnopharmacology is relatively new. It was born from a dramatic post-WWII change in the socio-cultural landscape of Western culture, including the psychedelic revolution that happened in the 1960s and 1970s. A key part of this movement was the hallucinogenic plants and fungi from Mexico, including plants such as Salvia Divinorum commonly called "sage of the diviners".

One of the most impactful regions of ethnopharmacology research was in Mexico. This essay covered some of the pioneer research in this field, highlighting what early researchers discovered and their areas of interest. In 1962 ethnopharmacologists Albert Hoffman and Gordon Wasson undertook exploration in Mexico, with Maria Sabina becoming their main informant linking them with Mazatec peoples. Three main plants are still used today as part of a Mazatec spiritual ceremonies including Psilocybe spp. mushrooms, the seeds from Ipomoea violacea L. (morning glory), and the leaves of S. divinorum.

Salvia is tended to in secret gardens by medical practitioners known as curandero (male) or curandera (female). These healers are led through a series of progressive visions by an experienced teacher, using plants such as salvia. These plants are taken at regular intervals to integrate the knowledge they have gained over the two years training to become a healer. In ceremony the plant is either decocted in water or the leaves are eaten. People have visions and then after they are "debriefed" to explain the meaning of their visions.

After attending many ceremonies and rituals, and recording plants Hoffman and Wasson were able to obtain a flowering specimen. Much research was able to be conducted and it was discovered this psychoactive plant's active compound was Salvinorin A. The plant has not had much attention compared to other hallucinogens; however, research shows that it is a non-nitrogenous kappa-opioid receptor selective agonist.

Being one of the last essays in the second volume of the symposiums literature, this piece and the those previous demonstrate the wide and variable array of research that has been conducted. However, one of the field's key criticisms is the accusation of exploiting local knowledge with no fair trade of benefits. In response to those less ethical, scientists have banded together to create international agreements. These include the Declaration of Belem, and the international legally binding Nagoya Protocol to call for the recognition of indigenous rights, ethics and research standards for the betterment of all parties involved, human or not.

Currently ethnopharmacology is thriving with its shift from a focus on searching for psychoactive drugs to other priorities. It is the hope that ethnopharmacological research will provide more and better scientific evidence for cultural medicines. Also, that the field will help empower everyone involved as well as to embrace traditional knowledge. What remains clear though is that ethnopharmacology must always be interdisciplinary or preferably transdisciplinary. As modern living severs human connection to nature, and as we reap the consequences it seems the "marrying of modern science and ancient wisdom" are more relevant than ever.