The potential of psychedelics for the treatment of Alzheimer's disease and related dementias.

Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressive neurodegenerative disease, demanding consideration of therapeutically relevant natural products and their synthetic analogues. This paper reviews evidence for effectiveness of natural and synthetic psychedelics in the treatment of AD causes and symptoms. The plastogenic effects of serotonergic psychedelics illustrate that they have efficacy for addressing multiple facets of AD pathology. We review findings illustrating neuroplasticity mechanisms of classic (serotonergic) and non-classic psychedelics that indicate their potential as treatments for AD and related dementias. Classic psychedelics modulate glutamatergic neurotransmission and stimulate synaptic and network remodeling that facilitates synaptic, structural and behavioral plasticity. Up-regulation of neurotrophic factors enable psychedelics to promote neuronal survival and glutamate-driven neuroplasticity. Muscimol modulation of GABAAR reduces Aß-induced neurotoxicity and psychedelic Sig-1R agonists provide protective roles in Aß toxicity. Classic psychedelics also activate mTOR intracellular effector pathways in brain regions that show atrophy in AD. The potential of psychedelics to treat AD involves their ability to induce structural and functional neural plasticity in brain circuits and slow or reverse brain atrophy. Psychedelics stimulate neurotrophic pathways, increase neurogenesis and produce long-lasting neural changes through rewiring pathological neurocircuitry. Psychedelic effects on 5-HT receptor target genes and induction of synaptic, structural, and functional changes in neurons and networks enable them to promote and enhance brain functional connectivity and address diverse mechanisms underlying degenerative neurological disorders. These findings provide a rationale for immediate investigation of psychedelics as treatments for AD patients.

Psychedelics, Sociality, and Human Evolution.

Our hominin ancestors inevitably encountered and likely ingested psychedelic mushrooms throughout their evolutionary history. This assertion is supported by current understanding of: early hominins' paleodiet and paleoecology; primate phylogeny of mycophagical and self-medicative behaviors; and the biogeography of psilocybin-containing fungi. These lines of evidence indicate mushrooms (including bioactive species) have been a relevant resource since the Pliocene, when hominins intensified exploitation of forest floor foods. Psilocybin and similar psychedelics that primarily target the serotonin 2A receptor subtype stimulate an active coping strategy response that may provide an enhanced capacity for adaptive changes through a flexible and associative mode of cognition. Such psychedelics also alter emotional processing, self-regulation, and social behavior, often having enduring effects on individual and group well-being and sociality. A homeostatic and drug instrumentalization perspective suggests that incidental inclusion of psychedelics in the diet of hominins, and their eventual addition to rituals and institutions of early humans could have conferred selective advantages. Hominin evolution occurred in an ever-changing, and at times quickly changing, environmental landscape and entailed advancement into a socio-cognitive niche, i.e., the development of a socially interdependent lifeway based on reasoning, cooperative communication, and social learning. In this context, psychedelics' effects in enhancing sociality, imagination, eloquence, and suggestibility may have increased adaptability and fitness. We present interdisciplinary evidence for a model of psychedelic instrumentalization focused on four interrelated instrumentalization goals: management of psychological distress and treatment of health problems; enhanced social interaction and interpersonal relations; facilitation of collective ritual and religious activities; and enhanced group decision-making. The socio-cognitive niche was simultaneously a selection pressure and an adaptive response, and was partially constructed by hominins through their activities and their choices. Therefore, the evolutionary scenario put forward suggests that integration of psilocybin into ancient diet, communal practice, and proto-religious activity may have enhanced hominin response to the socio-cognitive niche, while also aiding in its creation. In particular, the interpersonal and prosocial effects of psilocybin may have mediated the expansion of social bonding mechanisms such as laughter, music, storytelling, and religion, imposing a systematic bias on the selective environment that favored selection for prosociality in our lineage.

The Evolved Psychology of Psychedelic Set and Setting: Inferences Regarding the Roles of Shamanism and Entheogenic Ecopsychology.

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.

Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca.

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and ß-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.

Identifying the nature of shamanism.

Singh conflates diverse religious statuses into a single category that includes practitioners with roles that differ significantly from empirical characteristics of shamans. The rejection of biological models of trance and conspicuous display models misses the evolutionary roots of shamanism involving the social functions of ritual in producing psychological and social integration and ritual healing.

The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary Psychology.

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).

The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization.

Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are ß-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.

Religion and intergroup conflict: findings from the Global Group Relations Project.

How might religion shape intergroup conflict? We tested whether religious infusion-the extent to which religious rituals and discourse permeate the everyday activities of groups and their members-moderated the effects of two factors known to increase intergroup conflict: competition for limited resources and incompatibility of values held by potentially conflicting groups. We used data from the Global Group Relations Project to investigate 194 groups (e.g., ethnic, religious, national) at 97 sites around the world. When religion was infused in group life, groups were especially prejudiced against those groups that held incompatible values, and they were likely to discriminate against such groups. Moreover, whereas disadvantaged groups with low levels of religious infusion typically avoided directing aggression against their resource-rich and powerful counterparts, disadvantaged groups with high levels of religious infusion directed significant aggression against them-despite the significant tangible costs to the disadvantaged groups potentially posed by enacting such aggression. This research suggests mechanisms through which religion may increase intergroup conflict and introduces an innovative method for performing nuanced, cross-societal research.

Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca.

Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950's and 1960's they were largely prohibited in medical treatment and human research starting in the 1970's as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable "after-glow" effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics' well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.

A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

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.

Drug tourism or spiritual healing? Ayahuasca seekers in Amazonia.

This research addresses the question of whether Westerners who seek traditional spiritual medicine known as ayahuasca can be best characterized as "drug tourists" or as people pursuing spiritual and therapeutic opportunities. Participants in an ayahuasca retreat in Amazonia were interviewed regarding their motivations for participation and the benefits they felt that they received. These findings from the interviews were organized to reveal common motivations and benefits. Contrary to the characterization as "drug tourists", the principal motivations can be characterized as: seeking spiritual relations and personal spiritual development; emotional healing; and the development of personal self-awareness, including contact with a sacred nature, God, spirits and plant and natural energies produced by the ayahuasca. The motivation and perceived benefits both point to transpersonal concerns, with the principal perceived benefits involving increased self awareness, insights and access to deeper levels of the self that enhanced personal development and the higher self, providing personal direction in life.

El shamanismo como neuroteología / shamanism as neurotheology

El concepto del shamanismo es presentado, tanto a partir de las investigaciones transculturales como de los enfoques biológicos que explican las prácticas universales, sobre la base de una psicología evolutiva. El éxtasis, los rituales comunales, las relaciones con los espíritus y los poderes naturales están relacionados con los módulos cerebrales innatos y su integración adaptacional en las prácticas shamánicas. El éxtasis del shamanismo incluye la actividad de patrones de ondas cerebrales que incrementan los procesos de las estructuras paleomamíferas. Por su parte, los rituales comunales promueven los lazos grupales y estimulan los sistemas opioides, reforzando el sistema inmunológico. Los espíritus son representaciones de las funciones innatas de la conciencia el Yo, los otros, los agentes, integradas dentro de los complejos psicosociales que constituyen una psicología indígena. Por último, las actividades rituales desarrollan estas estructuras integrándolas en una terapia. Los poderes naturales explotan un módulo innato de diferenciación y clasificación social; y, asimismo, diversas dinámicas de yo otros subyacen en el vuelo mágico y las experiencias de muerte renacimiento. Por todo esto, los fundamentos biológicos del shamanismo demuestran su continua manifestación en las prácticas de curación contemporáneas.

El shamanismo como neuroteología / shamanism as neurotheology

El concepto del shamanismo es presentado, tanto a partir de las investigaciones transculturales como de los enfoques biológicos que explican las prácticas universales, sobre la base de una psicología evolutiva. El éxtasis, los rituales comunales, las relaciones con los espíritus y los poderes naturales están relacionados con los módulos cerebrales innatos y su integración adaptacional en las prácticas shamánicas. El éxtasis del shamanismo incluye la actividad de patrones de ondas cerebrales que incrementan los procesos de las estructuras paleomamíferas. Por su parte, los rituales comunales promueven los lazos grupales y estimulan los sistemas opioides, reforzando el sistema inmunológico. Los espíritus son representaciones de las funciones innatas de la conciencia el Yo, los otros, los agentes, integradas dentro de los complejos psicosociales que constituyen una psicología indígena. Por último, las actividades rituales desarrollan estas estructuras integrándolas en una terapia. Los poderes naturales explotan un módulo innato de diferenciación y clasificación social; y, asimismo, diversas dinámicas de yo otros subyacen en el vuelo mágico y las experiencias de muerte renacimiento. Por todo esto, los fundamentos biológicos del shamanismo demuestran su continua manifestación en las prácticas de curación contemporáneas.(AU)

Complementary therapy for addiction: "drumming out drugs".

OBJECTIVES: This article examines drumming activities as complementary addiction treatments and discusses their reported effects. METHODS: I observed drumming circles for substance abuse (as a participant), interviewed counselors and Internet mailing list participants, initiated a pilot program, and reviewed literature on the effects of drumming. RESULTS: Research reviews indicate that drumming enhances recovery through inducing relaxation and enhancing theta-wave production and brain-wave synchronization. Drumming produces pleasurable experiences, enhanced awareness of preconscious dynamics, release of emotional trauma, and reintegration of self. Drumming alleviates self-centeredness, isolation, and alienation, creating a sense of connectedness with self and others. Drumming provides a secular approach to accessing a higher power and applying spiritual perspectives. CONCLUSIONS: Drumming circles have applications as complementary addiction therapy, particularly for repeated relapse and when other counseling modalities have failed.