Whole Organisms or Pure Compounds? Entourage Effect Versus Drug Specificity

Abstract

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The "entourage effect" refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics. As Western medicine discovers the medicinal properties of whole organisms deemed sacred by traditional cultures, a fierce debate has been set between proponents of the use of purified chemicals versus supporters of long-established ritual uses of plants, fungi, and animals. As a professional neuroscientist with an interest in psychedelic medicines, it is clear to me that the attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with a plethora of interactions (Dos Santos et al., 2012; Mckenna, Towers, & Abbott, 1984). Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to

Variability in the Chemical Composition of a New Aromatic Plant Artemisia balchanorum in Southern Russia

“…Finally, the question of how best to extract and separate pure compounds and select for special chemotypes of lemon wormwood corresponds with the concept of the “entourage effect”, better known from cannabis studies [ 33 , 34 ]. This effect refers to the synergistic mode of multiple compounds, which may potentiate pharmaceutical efficacy.…”

Altered States of Consciousness During Ceremonial San Pedro Use

“…Hence, the question remains how changes in consciousness that accompany San Pedro consumption manifest when doses of mescaline and alkaloids are parametrically controlled. Finally, not all ceremonies were exclusive in terms of drugs that were consumed, signaling a potential entourage effect -the synergistic effect of polysubstance use on human consciousness (Ribeiro, 2018). One practitioner offered participants the opportunity to smoke mapacho, a nicotinecontaining leaf which is used by some Amazonian tribes as a plant medicine in ceremonial context (Sharrock, 2018), while two organizations allowed for the ingestion of cannabis in addition to San Pedro when participants were familiar with the effects and had regularly used cannabis before.…”

Why was early therapeutic research on psychedelic drugs abandoned?

“…We can also expect arguments to be made for allowing patients to use plant-based psychedelic drugs, such as mushrooms, ayahuasca and ibogaine, because of the putative ‘entourage’ effects of the whole plant (e.g. Ribeiro, 2018). These claims appeal to a popular cultural meme that ‘natural’ medicines derived from whole plants are safer and more effective than ‘synthetic’ pharmaceuticals, a meme often used by the ‘medical cannabis’ industry.…”