Chapter 2

Altereb Conaciommeaa anbDmga in Human Evolution

Michael Winkelman

Michael Winkelman, PhD (University of California-Irvine) retiredlrom the School ol Human Evolution and Social Change at ArizonaState University in 2009. He was president of the Anthropologyof Consciousness section of the American AnthropologicalAssociation, and was the lounding president ol its Anthropologyof Religion Section. Winkelman has engaged in cross-culturaland interdisciplinary research on shamanism and altered statesof consciousness, locusing principally on the universal patternsof shamanism and identifying the associated biological bases. Hisprincipal publications on shamanism include Sliamans, Priests,and Witches (1992), which provides a cross-cultural examinationof the nature of shamanism, and Slmmanisrn: A BiopsychosocialParadigm of Consciousness and Healing (originally 2000, 2nd editionZ010). Shamanism provides a biological model ol shamanism thatexplains the evolutionary origins ol spiritual healing in ancient ritualcapacities. This biogenetic structuralist approach is expanded in anassessment of the evolutionary origins ol religion in his coauthored

$9 Z3 W

liN'l'HEO(.iiEN5 ANI} 'l'Hl'I l)l€Vlil-OPl‘vIl'§N'|' OF CUl-TL.lRl'I

Supernatural as Natural (with john Baker, 2008). These approachesprovide a framework for understanding the necessary role ofpsychedelics in human evolution and their continued applicationin healing (also see Psychedelic Medicine [Z007], co-edited withTom Roberts). Winkelmans work has shown that shamanism andpsychedelics have a deep intersection in human evolution; thesecapacities for altering consciousness continue to be an importantpart of human experience and well-being today, as evidencedin the multidisciplinary Altering Consciousness (2011), which hecoedited with Etzel Cardena. Winkelman is currently living nearPirenopolis, in the central highlands of Brazil, where he is engagedin developing permaculture-based intentional communities. He canbe contacted at michaeljwinkelman@gmail.com or through Skype:michaeljwinkelman. His website is www.michaelwinkelman.com.

Introduction

The worldwide association of plant drugs that profoundly alterconsciousness with religious and spiritual activities (see de Rios1984, Schultes and Hoffman 1979, Ratsch 2005) points to intrinsicrelationships among the innate properties of our neurotransmissionsystems, altered consciousness, and in some cases, our addictivepotentials. But unlike the addictive properties of opiates, thesubstances used in spiritual traditions worldwide have a differentdynamic. Instead, these exogenous sources of neurotransmittersubstances are thought to be the origin of many cultures’ mostimportant deities and the origins of their spiritual and consciousness-transforming practices. Explaining the roles of the external sourcesof altered consciousness at the core of many spiritual traditions mustaddress the relationships of the variety of agents and activities thatprovoke them to the brain systems that are activated.

The differences between drug and non-drug alterations ofconsciousness are generally presumed to be so obvious that theircommon substrate is not considered. But the phenomenologicalsimilarities of drug and natural mystical experiences was illustrated

Lop no ‘Ii J rr"ttcr| tl

Al-TERiEl'J f.lUl\lSClUL.|S;\’li5S ANIJ [)RU(iS IN l'lUlvl:’t1\3E\»'Ul.l.J"l'lUN

in the double-blind study by Griffiths et al (2006) that showedpsilocybin produced the characteristic features found in naturallyinduced mystical experiences. These similarities remind us of thecommon substrate in the brain and neurotransmitters that underlieall experiences of altered consciousness, irrespective of their originsor interpretations.

The relationships among natural and drug-induced alterations ofconsciousness must be understood from an evolutionary perspective.This reveals altered consciousness to be related to endogenousmechanisms, which are triggered by both ancient evolutionaryadaptations andmore recently acquired propensities to use exogenoussources of substances to alter consciousness. Reconceptualizing plant“toxins” as “rewards” in terms of effects on behavior, emotions, andcognition reframes this human attraction as involving adaptations.These adaptations involved an enhanced ability to utilize exogenoussources of important endogenous neurotransmitter substances,as well as more sensitive neurotransmitter receptor systems, forusing these chemicals that have such profound effects on humanconsciousness.

Dopamine and Altered Consciousness

A central feature of the neural transmitter systems involved inaltered consciousness is the dopamine system, which is stimulatedby an enormous variety of chemicals (Previc 2009). Evolutionaryapproaches to use of drugs focus on the reward and reinforcementeffects they have on the dopamine system; virtually all classes ofdrugs (including alcohol, nicotine, stimulants, and THC) haveeffects on dopamine transmission in the limbic system, as well as onserotonergic transmission (Smith and Tasnadi 2007; Mandell 1980).The effects of endogenous opioids on dopaminergic transmissioninvolve similar dynamics for “not only opiates, but also alcohol,nicotine, cocaine, amphetamines, and A-9 tetrahydrocannabinol"(Smith and Tasnadi 2003, p. 21). Although they act through avariety of intermediary systems (serotonin, encephalins, GABA),

Lop no ‘Ii J rr"ttcr| tl

liN'l'HEO(.iiENS AN!) THE l)l'lVlil-l.)l’l‘vIl"1N'|' OF CUl-'l'L.lRl'I

acute exposure to the major categories of drugs of abuse results inincreases in dopaminergic activity, speci cally in the hippocampusand nucleus accumbens (Smith 1999).

The effects on dopamine receptors are typically characterized asunconditioned pleasurable responses that reinforce behaviors thatfavor successful adaptation, such as food and sex. In addition tothe naturally pleasurable effects, opioids reduce pain avoidanceand sexual behavior, and increase eating (Smith and Tasnadi 2007).The mesolimbic dopamine system and its rewarding properties andmediation of pleasures from natural rewards (food, sex) declinewhen the dopaminergic system is suppressed or impaired (Barbanoand Cader 2007). Salamone and Correa (2002) re ned this view inproposing that it is the dopamine system that attributes incentivequalities to a reward, potentiating the organisms associatedresponses. Humans’ addictive potential reflects the ability of thesame reward systems used to reinforce fitness—-enhancing behaviorssuch as eating and sex to be stimulated by other signals that elicitintrinsic feelings of well-being. They can also produce the powerfulexperiences that epitomize the importance of altered consciousnessin a cultures spiritual traditions found worldwide.While dopamine is associated with sex and other pleasurable

states, it does not appear to have a central role in emotional arousalin general, or social warmth and empathy, which instead dependon serotonin, norepinephrine (NE), opioids, and oxytocin (Previc2009). In contrast, high levels of dopamine lead to emotionaldetachment. Endogenous opioid is a general term referring to aclass of natural substances in the body that include endorphins,encephalins, dynorphins, and other opiate-like substances (Smithand Tasnadi 2003) that interact with the dopamine system. Thesesubstances, particularly Bi‘-endorphin, are functionally identical(analogues) to the opiates found in plants, which have the capacityto interact with the same neurotransmitter sites in our brains. Theendorphins are also adaptations for reducing pain and stress andenhancing learning and memory. The uniquely human activities oflong-distance running produce enhanced release of endorphins,

Lop no1tr.l rratcrt tl

Al-TERiEl'J f.lUNSCl£'JL.|S;\’li5-5 ANIJ l)RLl(i$ IN l'lUlvlAl\3 l§\»'l.'}l.U'l'lUN

extending the capacities of such extreme physical activity that wasadaptive in flight from predators, with the pain-numbing effectsfacilitating the ability to continue to flee rather than succumb to pain,muscle cramps, shortness of breath, etc. (Jones 2005). These effectsgo beyond the endorphins, forming part of the general sympatheticresponse.

The human dopamine system must be contextualized in broadevolutionary terms as part of our mammalian heritage, withsimilar effects across mammalian species in social bonding, frommother-infant bonds to broader social groups. The endogenousopioids that stimulate our reward and learning systems also havecore functions in the mammalian brain and its emotional, social,and self systems, especially breastfeeding and bonding. Sullivan,Hagen, and Hammerstein (2008) suggest that the central role ofthese substances in the mesolimbic dopamine system indicates thatwe should also understand the broader functions of the opioids inregulation of attention, the integration of sensorimotor behavior,and modi cation of behavioral programs. Previc (2009) reviewsevidence that dopamine is also vital for all of the key functions ofadvanced intelligence and cognition, including: programming andexecuting motor planning; workingmemory and capacity for parallelprocessing; spatial and temporal abstraction; cognitive flexibilitylmental set shifting; temporal sequence processing; and creativitylgenerativity.

Previc notes that all of these higher cognitive functions areconcerned with processing of information in distal space and tirne.Dopamine functions are linked to the brains ability to dealwith objects and events distant in space and time. Not onlyare dopaminergic circuits active during exploration of noveltyand reward learning, they result in prolonged effort for delayedgrati cation and pursuit of goal-directed responses. Dopamineappears central to understanding causal and temporal relationships.The abilities for context-independent cognition are exempli ed inthe capacities for “off-line thinking“ and “mental time travel,“ theability to experience and think about things other than those in the

Lop nq1tr.l rratcrt tl

liN'l'HFO(.iiEN5 ANI} THE l)l€Vlil-l.)l’l‘vIl'§l\I'|' OF CUl-TL.lRl'I

here and now. “In essence, ventromedial dopaminergic activationresults in the ‘triumph’ of extrapersonal brain activity over the bodysystems that anchor our self-concept and our body orientation aswell as a triumph over the more ‘rational’ executive intelligencemaintained in the lateral dopaminergic systems" (Previc 2009: 53).The ability for extrapersonal responses or cognition is exempli edin the capacities for “mental time travel." Winkelman (2010) reviewsresearch regarding these abilities for extrapersonal projection andillustrates how these extrapersonal functions of dopamine are keyto understanding central aspects of the shamanic soul flight or out-of-body experience, which exempli es the ability to have a context-independent consciousness of people and places far removed fromthe physical body.

“The predominance of dopamine in association with cortical areas,in which higher order sensory processing or cross-modal sensoryinteractions occur indicates that dopamine is especially well-suitedto making connections among stimuli and events and organizingthem into mental plans. This is bene cial in stimulating creativityand in ‘off-line‘ thinking and strategizing, important components ofabstract reasoning" (Previc 2009: 30). Dopamines central role in theintegrative functions of the prefrontal cortex is extended throughoutthe brain as the nervous system allows the pre-frontal cortex PFC toconnect to other cortical regions. The major dopaminergic systemsoriginate in the midbrain area, within the mesolimbic system andits numerous connections to other limbic structures and the frontalcortex. This system is the most important motivational system. Thesemidbrain and brainstem areas contain cell bodies, which producethe neurotransmitters and extend to all of the regions of the cortex.

Human Evolution and Drug Use

The dominant evolutionary approaches to explaining the humanpropensity for addiction characterizes these desires for consciousness-altering substances and succumbing to their addictive effects as theconsequence of a mismatch or discordance between our acquired

Cop no ‘llC.._l rratcrt tl

Al-TERiEl'J f.lOl'\lSClOL.|S;\’li5S ANIJ [)RU(iS IN l'lUlvl:’tl\* l'I\»'Ol.l.l'l'lO1"~l

tendencies and the current environment (e.g., Berridge 1996, Nesseand Berridge 1997; see Lende 2008). According to this view, drug-induced feelings that are linked to adaptive behaviors are the resultof our recent exposure to evolutionary novel drug substances.Harmful aspects of addiction result from a mismatch between ourinnate biological tendencies and the options for meeting those needsprovided by the environment. Drugs of abuse are thought to falselytrigger natural reward circuits and their sense of tness bene ts byblocking or short-circuiting the painful feelings that provide theadaptive functions of stimulating avoidance behaviors.

These perspectives have not considered the deeper evolutionaryroots of the relationships between our nervous systems and thesesubstances—which are both endogenous to our nervous systemand were also found in our ancient environments. The evolutionaryapproaches to addiction address the genetically based traits thatresult in behaviors that have effects in increasing tness (survivaland reproduction). Since drugs have generally been conceptualizedas causing problematic behaviors that reduce tness, the idea thattheir use may confer tness is initially counterintuitive. But this isthe result of a particular paradigmatic perspective.

Drug Use: Mismatch or Adaptation?

Sullivan, Hagen, and Hammerstein (2008) point to a variety of formsof evidence that illustrate problems with the predominant mismatchhypothesis. These substances are not new but were part of ancientenvironmental exposures that resulted in evolved counter-measuresto these plant defenses. A central problem is the paradox of thisconcept of drugs as sources of hedonistic rewards that stimulate ourreward systems because they have their role in ecological relations astoxins that inhibit consumption by poisoning those who consumethem. If the presence of these toxins in plants is an evolutionaryadaptation to deterring consumption by animals, why is it that thesesame substances are viewed as producing pleasurable rewards? Sinceanimals do not evolve genetic capacities to reward non-adaptive or

Cop no ‘llC.._l rratcrt tl

liN'l'HFO(.iiENS AN!) THE l)l'lVlil-Ol’l‘vIFN'|' OF CUl-'l'L.lRl'I

tness-reducing behaviors (rewarding the consumption of dangerousneurotoxins), Sullivan, Hagen, and Hammerstein conclude thathumans evolved in order to make use of these exogenous substances.

Several aspects ofdrug effects suggest an evolved capacity to bene tfrom these substances. In contrast to the debilitating effects generallyattributed to drugs, Smith (1999) illustrates there are a variety oftness bene ts to using these substances. Fitness bene ts may haveaccrued to our ancestors as a consequence of their ability to respondto these psychoactive substances. Across the diverse classes of plantdrugs there are effects of enhanced vigilance, the ability to ignorepain in the interest of survival activities, increased access to matingopportunities, reduction of apprehension and stress, feelings ofdetachment and euphoria, increased endurance and self-con dence,enhanced sensory and mental acuity, reduction of defensiveness,and reduction of depression and self-defeating activities. Clearlymany adaptive mechanisms could have been involved in humans‘physiological and cultural adaptations to environmental sources ofconsciousness-altering chemicals.

The effects of these toxins on the brains reward centers maybe an accident of plant-herbivore coevolution but also displayhallmark features of natural adaptations (Smith and Tasnadi 2003).A reciprocal relationship between food consumption and taste isprovoked by opioids—foods taste better when we are on opioids,and good-tasting food—sugars—cause a release of B-endorphin.Mammals evolved to eat foods with nutritional value, and the rarepresence of sugar in the aboriginal environment led to the selectionfor use of endogenous opioid release, to reinforce additional eatingbehavior. Gestational nutritional needs may have selected foropioid systems that induce fruit cravings and the many associatednutritional advantages of their consumption.De ning characteristics of humans, such as abstract, generative,

and context-independent cognition and other advanced mental skills,require dopamine as a neurotransmitter (Previc 2009). The use ofexecutive intelligence activates the dopamine system, and dopaminede ciencies are associated with a wide range of cognitive de cits.

Lop no itrd rratcrt tl

Al-'l'ERiEl'J l'.lONSClOL.|S:\’li5-S ANIJ l)RLl(i$ IN l'IUlvIAN l§\»'Ol.U'l'lON

Previc shows that dopamines effects must be related to humans‘evolved cognitive capacities, because dopamine is central to advancedintelligence, not only in humans but in other animals as well. Allspecies with advanced intelligence have concentrated dopamine,which may have been the only neurotransmitter that expandedthrough the evolution of primates and hominids. Furthermore,dopamine is highly concentrated in the prefrontal cortex, whichis Cl'11ClEll to humans’ higher order reasoning and planning (Previc2009: 15). The overall expansion of the dopaminergic system inprimates and humans led to increased concentrations in mostcortical regions, with high concentrations in the prefrontal andfrontal regions, especially in sensory processing areas where cross-modal integration occurs. Primates also evidence a greater densityof dopamine receptors in Level 1 of the cortex, the layer wherecoordination of activities underlying cognitive processes takes place.Dopamine and acetylcholine predominate as neurotransmitters inthe left hemisphere, which is the brain area managing these skills.

Previc notes that in the overall human evolution of thedopaminergic systems, there was a greater expansion of theprefrontal/striatal dopaminergic system relative to the mesolimbic!mesocortical pathways. He proposes that this allowed for thesublimation of basic impulsive mesolimbic drives and their controlby our rational intellect. Dopamine also plays a central role in goal-directed behavior, and has a role in dampening the physiologicalaspects of the stress response. This most important dopaminergicfunction reflects parasympathetic action on the autonomic nervoussystem ANS, dampening physiological arousal and increasingperipheral vasodilation (which has roles in erectile function and malesexual behavior). Dopamine also mediates pleasant and euphoricstates, but appears to have greater importance in inhibiting negativeemotional arousal of fear and anxiety, leading to a greater sense ofcontrol, an internal locus of control. This ability to use dopamine asa stress-reducer enables highly dopaminergic individuals to functionmore effectively in extreme environments (Previc 2009: 36), sincedopamine helps in managing stress by assisting in active coping.

Cop no ‘llC.._l rratcrt tl

32 liN'|'HFO(.iENS AND THE l)l€Vlil-Ol‘l‘vII'§N'l' OF CUl-'l'L.IRl'I

Drug Use and the Evolution of Consciousness

Sullivan and Hagen (2002) review evidence of a long-termevolutionary relationship between psychotropic plant substancesand humans’ cognitive capacities that indicates there were selectivebene ts of substance use. They characterize these bene ts in termsof the ability of plants to provide neurotransmitter analogues, whichserved as substitutes for endogenous transmitters that are rare orotherwise limited by dietary constraints. These are primarily inthe monoamine neurotransmitters such as serotonin, as well asacetylcholine, norepinephrine, and dopamine, which are crucialfor normal brain function and require dietary precursors. Theseneurotransmitters are central to managing stress, exerting selectivepressures for metabolic systems that utilize these exogenous sourcesof precursors for these neurotransmitters. Human genetic adaptationsto utilize these substances are illustrated in human-chimpanzeedifferences in neurotransmitter and neurohormone systems andresponses, particularly the opioids, dopamine and serotonin.

Human-Chimpanzee Differences in Drug Metabolismand Neurotransmitter Systems

The conservation of aspects of the dopamine and serotonergicneurotransmitter systems across evolution is manifested in their basicsimilarities across mammalian species; there were also enhancementsof these systems in human evolution. Genes that control proteinsequences in the brain have evolved much more quickly in humansthan chimpanzees (Shi, Bakewell, and Zhang 2006). Since thedivergence of hominids from our hominid ancestors, there has beenan accelerated evolution of and a positive selection for polypeptideprecursors and genes involved in opioid regulation (Wang et al2005, Rockman et al 2005). The uniquely human pituitary cyclase-activating polypeptide precursor (PACAP) that emerged duringhuman origins and since the time of separation from our commonancestor with chimpanzees underwent accelerated evolution only in

Lop non J rratcrr rl

Al-Tl€RiEl'J l'.lONSClOL.|SNlit5-S AND l)RLl(i$ IN l'IUlvlAN l§\»'l.'}l.U'l'lON

the human lineage (Wang et al 2005). The rapid evolution of PACAPprecursor genes was a consequence of positive selection, whichoccurred in the central regions of the gene, sites that have a criticalrole in enhancing the biological activity of neuropeptides throughprotecting them from enzymatic degradation and increasing theiraf nity for receptor binding (Wang et al 2005).

“The Chimpanzee Sequencing and Analysis Consortium“ (Wanget al 2005) found signi cant human and chimpanzee differencesthat indicate that there was a rapid evolutionary divergence in thehuman line involving xenobiotic metabolizing genes that provide anability to metabolize the plant toxins. Some of the most signi cantdifferences are in segmental duplication of genes, their repetitionin speci c areas of the genome. These gene duplications producechanges in the onset and extent of gene expressions, as well asmechanisms for a diversi cation of genes, which can occur duringduplication, providing a basis for novel functions (Wooding andjorde 2006).

The human CYPZD6 gene illustrates the adaptive functions that cancome from segmental duplication and its role in encoding an enzyme(cytochrome P450) involved in the metabolism of drugs. Sullivanet al (2008) point out that the mammalian xenobiotic-metabolizingcytochrome P450 provides evidence of a deep evolutionary historyof adaptation to plant toxins. Our ancestors underwent positiveselection for CYP2D, an enzyme that enables the body to metabolizeopiates, amphetamines, and other drugs, including plant toxins andserotonin reuptake inhibitors.

There have been waves of selective effects in the hominid line forgenes associated with opioid cis-regulation (Rockman et al 2005).The prodynorphin gene is found in chimpanzees as well, but it isexpressed to a far greater extent in humans. Natural selection resultedin an alteration of human prodynorphin, a signi cant precursormolecule for a range of endogenous opioids and neuropeptides.The evolution of humans involved natural selection for geneticmodi cations involving the ability to induce endogenous opioidprecursors. This selection for prodynorphin expression contributed

Lop no 1trJ rratcrr tl

34 IiN'l'HFO(.liENS ANI} THE l)l€VIil-Ol’lvII€N'|' OF CUl-'I'L.lRl'I

in signi cant ways to the evolution of human perception, emotion,and learning.Human evolutionary divergence from chimpanzees also involved

increases in expression of genes in regions involving regulatorygenes that duplicate copies of some genes. Oldham, I-Iorvath, andGeschwind (2006) characterize the chimp-human differences asinvolving an increased connectivity in the gene co-expressionnetworks in frontal brain networks of humans. Humans have anintensi cation of expression of genes associated with the CNS andthe frontal cortex innervations, particularly circuitry underlyinghigher cognitive processes.Highly dopaminergic minds are active, above average in

intelligence, achievement-oriented and goal seeking, and con dentin their abilities (Previc 2009). This is the positive side of thedopaminergic mind; there is also a dark side. This is illustrated inthe numerous pathologies associated with de ciencies of dopamine.There are several different dopamine-mediated personality disorderslinked to one of two major dopaminergic systems (i.e., lateral andventromedial). The ventromedial dopaminergic system provokesintense unconstrained aggressive drives to achieve distant goals, thatis, an unleashing of the motivation drives associated with wanting. Italso stimulates the creative genius in a search for novel associationsamong stimuli. The stimulation of the lateral dopaminergic levelsthat enhances executive control and internal locus of control can atexcessive levels lead to delusions of grandeur and invincibility, andmagical ideation about abilities to control distant events, and others.

Serotonergic Systems and the Alteration ofConsciousness

Another neurotransmitter system involved in altered consciousnessis the serotonin system, the primary system that is affected bypsychedelics such as LSD and psilocybin. Dopamine and serotoninare the two most important amines, and play a complementary rolein balancing the functions of the brain and body. “[T]he serotonergic

Cop no 1tcJ rratcrr tl

Al-TERiEl'J lllONSClOL.|SNliS-S AND DRUGS IN l'IUlvlAN l'I\»'f.")l.U'l'lON

inhibition of dopamine release is arguably the clinically mostimportant neurochemical interaction in the brain particularlyin the ventromedial and limbic subcortical and cortical areas"(Previc 2009: 21). The right hemisphere and its serotonergic andnoradrenergic systems inhibit the left hemisphere and dopamine.

Environmental mechanisms selecting for enhancement of speci cneurotransmitter capacities involve the many genres and species ofpsilocybin-containing mushrooms found worldwide, in frequentassociation with spiritual traditions. These substances have powerfuleffects on consciousness through action on the serotonergicneurotransmitter systems, producing alterations of consciousnessthat typify human concerns with the soul and supernatural. Whilehumans and other animals tend to respond in similar ways todrugs, there are notable human-chimpanzee differences in self-administration of drugs. While laboratory chimps will generallyself-administer alcohol, heroin, cocaine, caffeine, nicotine, andother addictive substances, there is a notable class of drugs thatthey will not continue to self-administer-—the psychedelics (McKim1991). This is speci cally true for our closest animal relatives, thechimpanzees. These differences reflect evolved differences in theserotonergic binding properties of humans’ hominid ancestors.

Human-Chimpanzee Divergences in SerotonergicBinding

Raghanti et al (2008) review the wide range of evidence thatindicates that the role of serotonin (5HT) in support of highercognitive functions was modi ed in the course of human evolutionand contributed to our cognitive specializations. The central effectsof LSD and hallucinogenic drugs on 5-HT receptors indicate thatthese should be prime candidates for evolution of our capacityfor the spiritual experiences produced by these substances. Thereis significant phylogenetic variation between humans and chimpsthat appears to have substantial functional implications for ourcognitive processing capabilities. Humans do not have, however,

Lop non J rratcrr tl

IiN'l'HFO(.liENS AND THE l)l€VIil-Ol’l‘vII"1N'|' OF I'_IUl-'I'L.lRl'I

quantitative increases in serotonin innervations, in comparison tochimpanzees, although there are species differences in innervationspatterns. In many respects chimpanzees and humans are similar intheir differences with respect to the serotonergic systems of otherprimates, including having the serotonergic axons emanating fromthe median raphe nuclei and unique neuronal cells in cortical areasresponsible for processing emotional and cognitive information(Raghanti et al 2008).

Pregenzer et al (1997) report ndings that the human andchimpanzee 5-HTID receptor amino acid sequences do, however,differ. In comparison with chimps, human serotonergic ligands,including several indoles and ergots, have comparable, lownanomolar binding af nities and a remarkable degree of similarityin their binding pro les with other ligands, the agents that bindto receptor sites. Yet while the chimpanzee 5-HTID receptors showa high degree of similarity to human 5-HT“) receptors, there arechemical template differences that indicate molecular divergencesamong the 5-HT“) receptors of humans and chimpanzees (Pregenzeretal1997)

Pregenzer et al (1997) examined the similarity of humans,chimpanzees, other primates, and mammals in the displacement ofserotonin by various drugs. In spite of highly analogous responsesto indoles and ergots in the binding of a wide variety of subtypes ofserotonin and dopamine receptors across primates and mammals,there are notable human differences. Even though humans andchimpanzees do not signi cantly differ in serotonin dissociation,humans have signi cantly greater displacement (2.5 to 4 timesgreater) as compared with chimpanzees on the binding of LSDand the ergots metergoline and dihydroergotamine (Pregenzer etal 1997). This evidence is highly suggestive of the possibility thathumans evolved to more ef ciently process psychedelic drugs.

Lop no 1trJ rratcrr tl

Al-TERiEl'J lllONSClOL.|SNliS-S AND DRUGS IN l'IUlvlAN l'I\»'f.")l.U'l'lON

Exogenous Neurotransmitters: Psilocybin-ContainingMushrooms

Adaptations to the fungi in their environment, especially the toxicspecies of mushrooms, was a signi cant feature affecting homininevolution. The psychoactive fungi that our foragingancestors exploredas possible food items in their environments exerted a selectiveinfluence on hominid evolution. Psychedelic mushrooms wouldhave been invariably encountered in our ancestral past, especiallyin tropical regions, given their worldwide distribution. Species ofmushrooms containing psilocybin have been found around the world(Guzman, Allen, and Gartz 1998). The worldwide distribution ofneurotropic fungi used as sacraments in cultures around the worldis good evidence that such substances altered consciousness in waysthat induced spiritual experiences and contributed directly to thedevelopment of religious explanations and activities. The ancientencounter with these substances is manifested in religious andspiritual interpretations associated with mushrooms worldwide (seeSchultes and Hofmann, I979, Ratsch 2005). Hundreds of cultureshave been found in which a wide variety of psychoactive substancesare used in religions, particularly shamanistic traditions.

The objective ability of the psychedelics to induce mystical andspiritual experiences is attested to in controlled clinical studies.Since the famous “Good Friday“ experiment by Pahnke (1966), therehas been clinical evidence of the objective ability of psychedelicsto produce mystical alterations of consciousness. In this classicexperiment, seminary students at Harvard Divinity School tookpsilocybin or a placebo control. Most of the seminary students whoreceived psilocybin had the most profound spiritual experiencesof their lives and remained convinced even decades later that itwas the most profound spiritual experience of their very religiouslives. This ability of the chemical substrate to produce spiritualexperiences was recently con rmed in a study carried out at johnHopkins University by Grif ths et al (2006), which found that whenthe participants took psilocybin (as opposed to a control substance)

Lop non J rratcrr tl

IiN'l'HFO(.liENS AND THE l)l€VIil-Ol’l‘vII"1N'|' OF I'_IUl-'I'L.lRl'I

they had spiritual and mystical experiences that induced effects ontheir attitudes, moods, as well as their own experience of spirituality,which persisted for months afterward. Two-thirds of the psilocybingroup rated the experience among the most meaningful and spiritualexperiences of their entire life. They had signi cantly higher scoreson scales for introvertive mysticism, extravertive mysticism, internaland external unity, sacredness, intuitive knowledge, transcendenceof time and space, ineffability, experiences of oceanic boundlessness,and visionary structuralization. In addition, psilocybin participantsshowed signi cantly higher levels of peace, harmony, joy, and intensehappiness, an enhanced positive attitude and mood about life, andincreases in altruistic social behaviors.

These ndings indicate that these substances led human ancestorsto an enhanced capacity to experience spiritual and transcendentalconnections,special alterations ofconsciousness thatalso had adaptivesocial signi cance. These psychedelic-based cognitive experiencesconstitute a neurotheology a neurologically based theology derivedfrom properties of the neural system, manifested in a number ofsimilar features associated with the use of psychedelic substances incultures around the world (Dobkin dc Rios 1984; Winkelman 1996,2000, 2007). These features of psilocybin-induced experiences arealso central to shamanism (Winkelman 1992, 2000, 2010). Sinceshamanism constitutes a primordial worldwide form of religiouspractice, this suggests that it was the effects of these substances thatwere responsible for the initial emergence of spirituality and thecentral alterations of consciousness institutionalized in shamanistictraditions around the world.A signi cant aspect of these exogenous neurotransmitter sources,

illustrated in the effects of psilocybin-containing mushrooms, istheir intrinsic ability to induce an animistic worldview regardingconsciousness. This biologically based “neurotheology“ presentsa mystical view of the world that has been fundamental tothe understanding of consciousness for many cultures. Thisneurotheology reflects an adaptive feature of the ability to use theseplant-derived exogenous sources of neurotransmitters. Their effects

Lop no 1trJ rratcrr tl

Al-TERiEl'J lllONSClOL.|SNliS-S AND DRUGS IN l'IUlvlAN l'I\»'f.")l.l.l'l'lON

on the serotonergic nervous system and macro-level processingin the brain produces alterations of consciousness that have beencore to consciousness traditions. Their effects subjectively present amodel of consciousness as spiritual, multileveled, and transcendent,and consider the typical manifestations of altered consciousness tobe the most signi cant of all forms of consciousness.

Dance as an Adaptation for Altered States

One uniquely human behavior in which both serotonin and opioidswere involved is dance. While the uniquely human capacity fordance involves exaptations of capacities provided by bipedalismand mimesis (Donald 1991), it has signi cant precursors in othermammalian behaviors. The special signi cance of dance in thealteration of consciousness is reflected in its worldwide associationwith spiritual, artistic, and collective social practices and its core rolein the activities of shamanism.Bachner-Melman et al (2005) studied speci c gene polymorphisms

associated with people who are engaged intensively with creativedance performance. This enhanced genotype associated withprofessional dancers was also associated with serotonin transporters(SLC6A4) and an arginine vasopressin receptor (AVPR1a), which isactivated by opioids. Professional dancers had higher levels of bothof these gene frequencies than normal controls and professionalathletes; furthermore, the higher levels of these genes weresigni cantly associated with a measure of spirituality and alteredstates of consciousness (the Tellegren Absorption Scale).

Bachner-Melman et al hypothesize that the association ofAVPR1a and SLC6A4 with dance reflects a common basis in genesassociated with courtship and social communication and mediatedby personality factors reflecting the social communication and thespiritual facets of dancing. The association of dance and the AVPR1agene reflects the central role of communication and social relations inthe functions of dance, with the evolutionary linkages of the AVPR1agene and dance reflected in vasopressins role in vertebrate courtship

Cop no 1tcJ rratcrr tl

IiN'l'HFO(.llENS AND THE Dl€VIil-Ol’l‘vII€N'|' OF CUl-'I'L.lRl'I

behavior, maternal behavior, animal bonding, and romanticattachment in humans. Human dancing is part courtship and partsocial communication strategies that have a shared evolutionaryhistory with the mating displays and af liative behaviors of otheranimals, reflecting a common basis in conservative neurochemicaland genetic mechanisms across vertebrates (Bachner-Melman et al2005).

Adaptive Effects of Altered Consciousness

This coevolution of our capacities for using exogenousneurotransmitter substances and experiencing unusual forms ofconsciousness involved a variety of adaptive effects. As Sullivan etal (2008) note, these are rare neurotransmitter substances; mostrequire dietary precursors, and the capacity to metabolize and useexogenous sources of these substances provided intrinsic bene ts.These psychotropic plants are capable of producing a variety ofother adaptive effects as well. The toxic effects of their alkaloids ona wide range of intestinal worms would have contributed to humanhealth, likely contributing to the ubiquitous sense that these plantsare in some way “cleansing.” There are a range of physiologicaleffects as a function of dose, including increased awareness andattention, enhanced visual acuity and excitement, includingerection and sexual arousal (see Winkelman and Schultes, 1996 forreview). Psychotropic plants also provided adaptive advantages intheir integrative and informational properties associated with thealteration of consciousness (Winkelman 2007, 2010).

Mandel] (1980) suggests that the common biological basis ofdiverse procedures, agents, and conditions involve disinhibitingthe temporal lobe structures that result in the emotional floodingexperienced as ecstasy and visions from the “inner world.” Thehippocampal-septal system, whose activation is associated withthese effects, has terminal projections from the somatic andautonomic nervous systems that form part of an extensive systemof innervations connecting areas of the brain, in particular, linking

Lop non J rratcrr tl

ALTERIED l'.lONSClOL.|SNli5-S AND l)RLl(iS IN l'IUlvlAN f§\»'l.'}l.U'l'lON

the frontal cortex with the limbic system. The limbic system (thepaleomammalian brain) is that part of the brain where emotions areintegrated with memories. Enhancement of these processes withexogenous neurotransmitter analogues such as the DMT in psilocybinmushrooms illustrates their adaptive advantages associated withgroup bonding.Although the psychedelics are characterized by a number of

different chemical structures and modes of action, they producea number of common physiological effects through their effectson the serotonergic neurotransmitter system (see Passie et al2008; also see Aghajanian and Marek 1999). The major naturallyoccurring psychedelics (such as the mescaline-containing cactiand various genera of psilocybin-containing mushrooms) containphenylalkylamine and indole alkaloids similar in chemical structureto the neural transmitter serotonin, and have their effects onconsciousness and spiritual experiences by their interaction withserotonergic receptors. The role of serotonin as a “neuromodulator,”the structural similarity ofpsychedelics and serotonin, and the speci ceffects of the psychedelics on serotonergic transmission provide abasis for their recharacterization as “psychointegrators“ (Winkelman1996, 2001, 2007). While there are a number of different substancesthat produce hallucinogenic reactions in humans, those with a basisin action on serotonin act as psychointegrators, enhancing theintegration of information in the brain by releasing the functions ofareas central to managing processes related to fundamental aspects ofself, emotions, memories, and attachments. This psychointegrativeeffect is manifested physiologically in the typical effects on brainwaves produced by these substances, the stimulation of coherenttheta wave synchronization along the neuraxis, the central nervebundle linking the structural levels of the brain. The effects aremanifested psychologically in the experiences of healing, wholeness,interconnectedness, cosmic consciousness, and other transpersonalexperiences that these substances regularly produce.This integration of brain networks as a generic feature

underlying ASC is illustrated by Vollenweiders (1998) research

Lop no 1trJ rratcrr tl

IiN'l'HFO(.llENS AND THE l)l€VIil-Ol’l‘vII"1N'|' OF l'_IUl-'I'L.lRl'I

on the mechanisms of action of psychedelics on the major corticalloops. The frontal-subcortical circuits provide one of the principalorganizational networks of the brain involving neuronal linkagesand feedback loops of the cortical areas of the frontal brain with thethalamus of the brain stem region. These loops unite speci c regionsof the frontal cortex with lower brain regions, providing circuitsthat are central to brain-behavioral relationships, social actions,motivations, and executive functions. Vollenweider attributes theconsciousness-altering properties of psychedelics to their selectiveeffects on the brains cortico-striato-thalamo-cortical feedback loopsthat link the information-gating systems of lower levels of the brainwith the frontal cortex. These loops are regulated by the thalamus,which limits the ascending inforrnation to the frontal cortex fromthe environment and body. Psychedelics disable this disinhibitionprocess; this increases access to the flow of information that isordinarily inhibited, overwhelming the frontal cortex and leadingto an alteration of experience of self, other, environment, and theinternal world of psychological structures and projections.The effects of these substances upon neural, sensory, emotional,

and cognitive processes illustrate the adaptive advantages producedby the inhibition of the serotonergic systems. This involves anenhancement ofconsciousness provoked by increasing the integrativeinformation-processing, achieved by stimulation of the serotonergiccircuitry linking the lower structures of the brain (paleomammalianand reptilian). Psychointegrative effects derive from the disinhibitionof emotional and social processes and the stimulation of systemicintegration of brain functions, resulting in the integration oflimbic system emotional processes with the neocortical processes.This results from the loss of the inhibitory effect of serotonin onthe mesolimbic temporal lobe structures, leading to synchronousdischarges in the temporal-lobe limbic structures of the visual cortexexperienced as visions (Mandel 1980). The psychointegrators havethe effect of coupling nonlinguistic behavioral and social-emotionaldynamics with rational processes and result in a function integrationof the different systems of the brain.

Lop no 1trJ rratcrr tl

ALTERIED l'.lONSClOL.|SNli5-S AND l)RLl(iS IN l'IUlvlAN f§\»'l.'}l.U'l'lON

Conclusions

Both dopamine and serotonin are key to understanding thealterations of consciousness found worldwide in shamanistictraditions. Selection for enhanced opioid mechanisms over hominidevolution increased capacities in social, emotional, and cognitiveareas, exempli ed in group bonding rituals. Species of psilocybin-containingmushrooms found worldwide likely selected for enhancedserotonergic neurotransmitter systems, where the interference effectsof these substances produce alterations of consciousness that typifyhuman concerns with the soul and supernatural. These adaptationsare manifested in the universality of ritual practices directed atenhancing peoples access to these experiences (Winkelman 1992).Winkelman (2010) describes a variety of adaptive aspects of

drugs and the associated conditions of altered consciousness.One feature involves their ability to enhance access to normallyunconscious information and to integrate thought processes.These innate propensities produce an integration of different brainsystems, enhance learning of information and promote behavioral,emotional, and cognitive integration. Religious altered states ofconsciousness reflect an adaptive response involving enhancedintegration of information from unconscious processes of the mind,integrating the body-level awareness of the prelinguistic mind intoconsciousness. Religious experiences are encounters with our ownunconscious potential in ways that are directly accessible to personalconsciousness, enabling normally unconscious infonnation to beused in directing our adaptations to the environment. The functionalroles provided by the dream capacity are elicited both by shamanicritual as well as the exogenous opioid and serotonergic analogues.

The association of serotonin and the opioid system (vasopressin)with alterations of consciousness and mystical experiences, as wellas enhanced dance propensities, indicates a coevolution of thecapacities of dance and the capacities for altering consciousness.Clearly, dance has that capacity to induce alterations of consciousnessthrough a variety of mechanisms (such as stimulating the release

Cop no 1tcJ rratcrr tl

IiN'l'HFO(.llENS AND THE l)l€VIil-Ol’l‘vII"1N'|' OF l'_IUl-'I'L.lRl'I

of opioids, producing rhythmic stimulation of the brain, as well asinducing exhaustion and collapse; see Winkelman 2010). Furthergenetic adaptations involving the serotonergic and opioid systemsin dance are linked to the evolution of a set of uniquely humancapacities involving the expressive capacity of mimesis, the ability tointentionally represent through imitation. This body-based imagisticsystem of expression reflects a level of consciousness communicatedthrough a variety of expressive forms—such as play, drama, ritual,music, emotions, shamanic ritual, and ultimately human spiritualityand religion.

Previc (2006) contends that there is a common neuroanatomyand neurochemistry underlying phenomena such as dreaming,hallucinations, and extreme religious beliefs. The common neuralsubstrate involves dopamine, particularly elevated levels in theventromedial cortical areas. This corresponds to the anatomicalbasis of these phenomena, which he postulated to “be mediatedby ventromedial (cortico-limbic) pathways extending from themedial temporal lobe to the anterior cingulate and prefrontal cortex”(2006: 518). Previc notes that there are a number of psychologicaldisorders (i.e., bipolar disorder, obsessive compulsive disorder,and schizophrenia) that are: 1) associated with increased religiousactivity, experiences, or practices; and 2) involve an overactivationof dopamine, particularly in the left hemisphere. Furthermore, thebrain activity typical of disorders associated with hyper-religiosity,as well as dreams, hallucinations, paranormal experience, andparanormal behaviors, involve action in the ventromedial systemof extrapersonal functions, which is freed from inhibition by theprefrontal (focal-extrapersonal or executive) dopaminergic systemand/or posterior serotonergic (peripersonal) inputs (Previc).

Diverse forms of altering consciousness all involve this enhancedcapability to access the output of the unconscious mind and ourinnate cognitive modules. These capacities are elicited by manymechanisms, particularly in the visual system, where the effects ofvision-inducing plants are among the most prominent mechanisms.They enabled an extended exploitation of the visual associational

Lop no 1trJ rritcrr tl

r-’tl-'l'EREEl'J lllUNSClUL.|S?~iliS-5 A3\El)[)RU(i$l1\l l'lLlM:’tl\* E\»'Ul.l.J"l'|U1"~l

cortex and its ability to manage visual and other information. Thisexpanded associational area improved the brains capacity to interfacewith a variety of other neural mechanisms, including those involvedin learning, problem-solving, and memory formation.The role of drugs in the evolution of human consciousness must be

understood in relationship to effects on the serotonergic system andits roles in overall brain functioning. The alterations of consciousnessenhance paleomammalian brain functions and their coordinationand integration with the entire brain. Enhanced serotonergicmechanisms contributed to experiences of altered consciousnessin humans, embodied in visionary experiences. The recurrentfeatures of the mystical experiences induced by these substancesindicate that they reflect biological bases and neurognostic forms,biologically based aspects of knowing. These experiences re ectedan enhanced integration of unconscious processes and potentialsinto consciousness and the overall integration of brain processes.Human evolution was stimulated by interactions among exogenousneurotransmitter substances. the adaptive potentials of the statesof consciousness they produced, and the shamanic ritual practicesthat supported the engagement with altered states. The worldwideassociation of psychedelics with spiritual traditions re ects the abilityof these substances to produce profound alterations of consciousness.These alterations provide a basic neurophenornenological paradigmfor understanding the nature of altered consciousness.

Acknowledgments

l thank Fred Previc for his review of and suggestions on themanuscript.

Cop no 1tcJ n"ttcr| tl

fiN'l'HEO(.iiEN$ AN!) THE l)l'l‘v’Iil-OF'l‘vIl"1N'|' OF CUl-'l'L.lRl'I

References

Aghajanian, G., and G. Marek. 1999. “Serotonin and I-Iallucinogens,“Neur'opsychopharrnacology 21: 16S-23S.

Bachner-Melman, Rachel, Christian Dina, Ada H. Zohar, NaamaConstantini Elad Lerer. 2005. “AVPR1a and SLC6A4 GenePolymorphisms Are Associated with Creative Dance Performance."PLoS Genetics 1(3): e42.

Barbano, M. Flavia, and Martine Cader. 2007. “Opioids for HedonicExperiences and Dopamine to Get Ready for lt." Psychophnrmocolog1911497-506.

Berridge, K. 1996. “Food reward: Brain Substrates of Wanting andLiking," Neuroscience Biobehavioral Review 28:309-369.

Dietrich, Arne. 2003. “Functional Neuroanatomy of Altered Statesof Consciousness: The Transient Hypofrontality Hypothesis."Consciousness and Cognition 12: 231-256.

de Rios, Marlene Dobkin. 1984. Hallucinogens: Cross-CulturalPerspectives. Albuquerque: University of New Mexico.

Donald, Merlin. 1991. Origins of the Modern Mind. Cambridge, MA:Harvard University Press.

Griffiths, R. R., W A. Richards, U. McCann, and R. Jesse. 2006.“Psilocybin Can Occasion Mystical-Type Experiences HavingSubstantial, Sustained Personal Meaning and SpiritualSigni cance." Psychopharrnacology 187(3): 268-283.

Guzman, G., _I. Allen, and]. Gartz. 1998. “A Worldwide GeographicalDistribution of the Neurotropic Fungi, an Analysis and Discussion."Ann. Mus. civ. Rovereto 14:189-280.

Jones, P. 2005. “Ultrarunners and Chance Encounters with ‘AbsoluteUnitary Being.“ Anthropolog» of Consciousness 15(2): 39-50.

Lende, D. 2008. “Evolution and Modern Behavior Problems: The Caseof Addiction.” ln Evolutionary Medicine and Health, edited by W.Trevathan, E. Smith, and J. McKenna. Oxford: Oxford UniversityPress, pp. 277-290.

ff.-'UF:.'||"f_l|:| ‘ll J n"atcr| 1|

Al-TERfil'J lll(JNSClUL.|S:\’l§S-5 ANI) l)RU(i5- IN l'lLll*-*l:’tl\3 E\»'€.')l.U'I'IUN

Mandel], Arnold. 1980. “Toward a Psychobiology of Transcendence:God in the Brain." In The Psychobiology of Consciousness, pp. 379-464, edited by Julian Davidson and Richard Davidson. New York:Plenum.

McKim, W 1991. Drugs and Behavior An Introduction to BehavioralPharrnacology. Englewood Cliffs, NJ: Prentice-Hall.

Nesse, R. 1994. “An Evolutionary Perspective on Substance Abuse."Etholog and Sociobiology 15: 339-348.

Nesse, R. and K. Berridge. 1997. “Psychoactive DrugUse in EvolutionaryPerspective.“ Science 278: 63-66.

Oldham, M., S. Horvath, and D. Geschwind. 2006. “Conservationand Evolution of Gene Coexpression Networks in Human andChimpanzee Brains.” Proceedings of the National Academy ofSciencesof the United States ofAmerica. 103(47): 17973-17978.

Passie, T., I-Ialpern, J., Stichtenoth, D., Emrish, I-1., and Hintzen, A.2008. “The Pharmacology of Lysergic Acid Diethylamide: AReview.“ CNS Neuroscience 6» Therapeutics 14: 295-314.

Pahnke, W. 1966. Drugs and Mysticism, The International Journal ofParapsychology 8(2): 295-313.

Pregenzer, J., Alberts. G., Bock, J. Slightom, and W lm. 1997.“Characterization of Ligand Binding Properties of the 5-HT“)Receptors Cloned from Chimpanzee, Gorilla and Rhesus Monkeyin Comparison with Those from the Human and Guinea PigReceptors.” Neuroscience Letters 3(17) 117-120.

Previc, E 2006. “The Role of the Extrapersonal Brain Systems inReligious Activity.” Consciousness and Cognition 15: 500-539.

Previc, E 2009. The Doparninergic Mind in Human Evolution and History.Cambridge: Cambridge University Press.

Raghanti, M., C. Stimpson, E Marcinkiewicz, P. Hof, and C. Sherwood.2008. “Differences in Cortical Serotonergic Innervation amongHumans, Chimpanzees, and Macaque Monkeys: A ComparativeStudy.“ Cerebral Cortex 18: 584-597.

tsopvrnq 11 '-_l rratcn tl

IN I Hl*O(.1l NS AN!) THE l)l€\-’El-(.)I’l‘vIl€N'l' OF t'_IUl-'l'L.lRl'I

Ratsch, C. and John R. Baker, trans. (2005). The Encyclopedia ofPsychoactive Plants: Ethnopharmacologt and Its Applications.Rochester, VT: Park Street Press. Originally published as (1998)Enzyklopadie cler psychoaktiven P anzen. Aarau, Switzerland: ATVerlag.

Rockman et al. 2005. “Ancient and Recent Positive SelectionTransformed Opioid Cis-Regulation in Humans PLOS,“ Biologi3(12)I 2208-2219.

Salamone,J. and Correa, M. 2002. “Motivational Views ofReinforcement:Implications for Understanding the Behavioral Functions ofNucleus Accumbens Dopamine.” Behavioral Brain Research 137:3-25.

Schultes, R. and Hofmann, A. 1979. Plants of the Goals: Origins ofHallucinogenic Use. New York: McGraw Hill. (Reprinted 1992 byHealing Arts Press, Rochester, VT).

Shi, R, M. Bakewell, and J. Zhang. 2006. “Did Brain-Speci c GenesEvolve Faster in Humans Than in Chimpanzees?“ Trends Genet22: 608-613.

Smith, E. 1999. “Evolution, Substance Abuse, and Addiction." InEvolutionary Medicine, edited by E. Smith and]. McKenna, 375-40. New York: Oxford University Press.

Smith, E. and B. Tasnadi. 2007. “A Theory of Natural Addiction.“ Gamesand Economic Behavior 59: 316-344.

Sullivan, R., E. Hagen, and E Hammerstein. 2008. “Revealing theParadox of Drug Reward in Human Evolution. Proceedings of theRoyal Society B. 275: 1231-1241.

Sullivan, R. and E. Hagen. 2002. “Psychotrophic Substance-Seeking:Evolutionary pathology or adaptation?” Addiction 97: 389-400.

The Chimpanzee Sequencing and Analysis Consortium. 2005. “InitialSequence of the Chimpanzee Genome and Comparison with theHuman Genome.“ Nature 437: 69-87.

Vollenweider, F. 1998. “Recent Advances and Concepts in the Searchfor Biological Correlates of Hallucinogen-Induced Altered Statesof Consciousness.” Heffter Review of Psychedelic Research I: 21-32.

ll.-'l:lF:||"f_l|:| t clrratcn I

Al-TERfil'J lllUNSClUL.|S:\’liS-5 ANI) l)RLl(i§i- IN l'lLll*-*lAN li\»'Ul.U'I'If.IN

Wang et al. 2005. “Accelerated Evolution of the Pituitary AdenylateCyclase-Activating Polypeptide Precursor Gene during HumanOrigin.“ Genetics 170: 801-806 2005.

Winkelman, M. 1992. “Shamans, Priests, and Witches: A Cross-CulturalStudy of Magico-Religious Practitioners." Anthropological ResearchPapers #44. Arizona State University.

Winkelman, M. 1996. “Psychointegrator Plants: Their Roles inHuman Culture and Health" In Sacred Plants, Consciousness andI-IealingCross-Cultural and Interdisciplinary Perspectives: Yearbookof Cross-Cultural Medicine and Psychotherapy Volume 6, editedby M. Winkelman and W. Andritzky, pp. 9-53. Berlin: Verlag undVertrieb.

Winkelman, M. 2000. Shamanism: The Neural Ecology of Consciousnessand Healing. Westport, CT: Bergin and Garvey.

Winkelman, M. 2001. “Psychointegrators: Multidisciplinary Perspectiveson the Therapeutic Effects of Hallucinogens." ComplementaryHealth Practice Review 6(3): 219-237.

Winkelman, M. 2007. “Therapeutic Bases of Psychedelic Medicines:Psychointegrative Effects.” In Psychedelic Medicine, edited byM. Winkelman and T. Roberts, Vol. 1. Westport, CT: PraegerfGreenwood Perspectives.

Winkelman, M. 2010. Shamanism: A Biopsychosocial Paradigm ofConsciousness and Healing. Santa Barbara, CA: ABC-CLIO.

tsopvrnq If '-_l rratcn tl