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Neuropharmacological effects of psychedelics have profound cognitive, emotional, and social effects that inspired the development of cultures and religions worldwide. Findings that psychedelics objectively and reliably produce mystical experiences press the question of the neuropharmacological mechanisms by which these highly significant experiences are produced by exogenous neurotransmitter analogs. Humans have a long evolutionary relationship with psychedelics, a consequence of psychedelics' selective effects for human cognitive abilities, exemplified in the information rich visionary experiences. Objective evidence that psychedelics produce classic mystical experiences, coupled with the finding that hallucinatory experiences can be induced by many non-drug mechanisms, illustrates the need for a common model of visionary effects. Several models implicate disturbances of normal regulatory processes in the brain as the underlying mechanisms responsible for the similarities of visionary experiences produced by psychedelic and other methods for altering consciousness. Similarities in psychedelic-induced visionary experiences and those produced by practices such as meditation and hypnosis and pathological conditions such as epilepsy indicate the need for a general model explaining visionary experiences. Common mechanisms underlying diverse alterations of consciousness involve the disruption of normal functions of the prefrontal cortex and default mode network (DMN). This interruption of ordinary control mechanisms allows for the release of thalamic and other lower brain discharges that stimulate a visual information representation system and release the effects of innate cognitive functions and operators. Converging forms of evidence support the hypothesis that the source of psychedelic experiences involves the emergence of these innate cognitive processes of lower brain systems, with visionary experiences resulting from the activation of innate processes based in the mirror neuron system (MNS).

This review illustrates the relevance of shamanism and its evolution under effects of psilocybin as a framework for identifying evolved aspects of psychedelic set and setting. Effects of 5HT2 psychedelics on serotonin, stress adaptation, visual systems and personality illustrate adaptive mechanisms through which psychedelics could have enhanced hominin evolution as an environmental factor influencing selection for features of our evolved psychology. Evolutionary psychology perspectives on ritual, shamanism and psychedelics provides bases for inferences regarding psychedelics’ likely roles in hominin evolution as exogenous neurotransmitter sources through their effects in selection for innate dispositions for psychedelic set and setting. Psychedelics stimulate ancient brain structures and innate modular thought modules, especially self-awareness, other awareness, “mind reading,” spatial and visual intelligences. The integration of these innate modules are also core features of shamanism. Cross-cultural research illustrates shamanism is an empirical phenomenon of foraging societies, with its ancient basis in collective hominid displays, ritual alterations of consciousness, and endogenous healing responses. Shamanic practices employed psychedelics and manipulated extrapharmacological effects through stimulation of serotonin and dopamine systems and augmenting processes of the reptilian and paleomammalian brains. Differences between chimpanzee maximal displays and shamanic rituals reveal a zone of proximal development in hominin evolution. The evolution of the mimetic capacity for enactment, dance, music, and imitation provided central capacities underlying shamanic performances. Other chimp-human differences in ritualized behaviors are directly related to psychedelic effects and their integration of innate modular thought processes. Psychedelics and other ritual alterations of consciousness stimulate these and other innate responses such as soul flight and death-and-rebirth experiences. These findings provided bases for making inferences regarding foundations of our evolved set, setting and psychology. Shamanic setting is eminently communal with singing, drumming, dancing and dramatic displays. Innate modular thought structures are prominent features of the set of shamanism, exemplified in animism, animal identities, perceptions of spirits, and psychological incorporation of spirit others. A shamanic-informed psychedelic therapy includes: a preparatory set with practices such as sexual abstinence, fasting and dream incubation; a set derived from innate modular cognitive capacities and their integration expressed in a relational animistic worldview; a focus on internal imagery manifesting a presentational intelligence; and spirit relations involving incorporation of animals as personal powers. Psychedelic research and treatment can adopt this shamanic biogenetic paradigm to optimize set, setting and ritual frameworks to enhance psychedelic effects.

Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor (Sig-1R) agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: (1) the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and (2) on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the Sig-1R which can explain its widespread therapeutic indications.

Differences among constructivist, perennialist, and universalist perspectives on mystical experiences are bridged with neurophenomenology and neuroepistemology perspectives that illustrate constructivist and deconditioning processes and universal innate experiences. These approaches show that phenomenal similarities and differences in the features of meditative experiences are related to specific brain functions and processes. This illustrates that recurrent forms of mystical consciousness involve the activation or suspension of specific brain functions and their forms of knowing. Meditators’ deliberate modifications of brain processes engage constructivist and deconditioning processes that provide access to intrinsic states understood as mystical experiences. Deconditioning of habitual cognitive processes through meditation changes habitual attention and cognition, permitting access to preconceptual awareness and normally unconscious intrinsic mental processes. Different mystical experiences involve changes in specific neurologically mediated forms of self that provide the basis for universal forms of mystical experience. Neuroepistemological perspectives on qualia of meditative states and their relations to mental processes and brain features provide a framework for understanding recurrent forms of mystical experiences as natural brain states.

Calvin Chatlos provides a novel consideration of spiritual experiences and attempts to find ontological grounds to span these concerns within science, philosophy, and theology. Conceptualization of spiritual experiences in terms of self-worth presents interesting avenues for future considerations of the role of self in explaining spirituality but also faces several validity challenges. Resolving ontological issues requires first addressing epistemological issues regarding the nature of knowledge, which permits an interdisciplinary investigation of spirituality and the soul. The cross-cultural validity of such constructs requires their basis in neurophenomenology, neurognostic perspectives, and neurological processes that engage naturalist perspectives on the foundations of religion.

The relationship of wu (巫) to shamanism is problematic, with virtually all mentions of historical and contemporary Chinese wu ritualists translated into English as shaman. Ethnological research is presented to illustrate cross-cultural patterns of shamans and other ritualists, providing an etic framework for empirical assessments of resemblances of Chinese ritualists to shamans. This etic framework is further validated with assessments of the relationship of the features with biogenetic bases of ritual, altered states of consciousness, innate intelligences and endogenous healing processes. Key characteristics of the various types of wu and other Chinese ritualists are reviewed and compared with ethnological models of the patterns of ritualists found cross-culturally to illustrate their similarities and contrasts. These comparisons illustrate the resemblances of pre-historic and commoner wu to shamans but additionally illustrate the resemblances of most types of wu to other ritualist types, not shamans. Across Chinese history, wu underwent transformative changes into different types of ritualists, including priests, healers, mediums and sorcerers/witches. A review of contemporary reports on alleged shamans in China also illustrates that only some correspond to the characteristics of shamans found in cross-cultural research and foraging societies. The similarities of most types of wu ritualists to other types of ritualists found cross-culturally illustrate the greater accuracy of translating wu as “ritualist” or “religious ritualist.”

N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.[PUBLICATION ABSTRACT]