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The ethnobotany of psychoactive plant use: A phylogenetic perspective

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Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests multiple ethnobotanical origins and widespread human dependence on these plants, motivating pharmacological investigation into their potential as modern therapeutics for various neurological disorders.
The phylogeny (cladogram) of traditionally used psychoactive plant taxa. The phylogeny conforms to expected groupings (APG IV, 2016). The 11 main plant families are highlighted (top to bottom): Myristicaceae, Papaveraceae, Malvaceae, Fabaceae, Cactaceae, Asteraceae, Convolvulaceae, Solanaceae, Lamiaceae, Rubiaceae, Apocynaceae. Grey circles next to their family names are proportional to total generic diversity within the family with lowest count for Myristicaceae (21 genera), and highest with 1623 genera for Asteraceae (Christenhusz & Byng, 2016). Branches are coded according to the different cultures (Native American: red solid line; Middle Eastern and African: orange dashed line; European: blue solid line; Indomalayan: green dotted line; Temperate Asia: pink solid line, Australasia: yellow solid line; Multicultural: grey solid line). Branches in bold represent bootstrap node support >50% and SH-like branch support >0.9. Psychoactive uses were overlain next to taxon names in columns (Ha, hallucinogen; Sm, stimulant; Ax, anxiolytic; Ad, antidepressant; Sd, sedative; Ag, analgesic; Ap, aphrodisiac; along with the primary neurotransmitters affected by the phytochemical/s exerting the dominant psychoactive effect (delineated with boxes; cf. Table 2). Shaded plant families with phytochemicals that activate certain neurotransmitter systems (e.g., receptor agonists) show the neurotransmitter/s involved with green (bright) background; phytochemicals with inhibitory effects to the NT have red (dark) background. In Asteraceae, neuropharmacology is unclear (???).
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Submitted 28 June 2016
Accepted 9 September 2016
Published 5 October 2016
Corresponding author
Jeanmaire Molina,
jeanmaire.molina@liu.edu
Academic editor
Michael Wink
Additional Information and
Declarations can be found on
page 23
DOI 10.7717/peerj.2546
Copyright
2016 Alrashedy and Molina
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Creative Commons CC-BY 4.0
OPEN ACCESS
The ethnobotany of psychoactive plant
use: a phylogenetic perspective
Nashmiah Aid Alrashedy*and Jeanmaire Molina*
Department of Biology, Long Island University, Brooklyn, NY, United States
*These authors contributed equally to this work.
ABSTRACT
Psychoactive plants contain chemicals that presumably evolved as allelochemicals but
target certain neuronal receptors when consumed by humans, altering perception,
emotion and cognition. These plants have been used since ancient times as medicines
and in the context of religious rituals for their various psychoactive effects (e.g., as
hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various
cultures motivates investigation of the commonalities among these plants, in which
a phylogenetic framework may be insightful. A phylogeny of culturally diverse psy-
choactive plant taxa was constructed with their psychotropic effects and affected neu-
rotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows
multiple evolutionary origins of psychoactive families. The plant families Myristicaceae
(e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae
(morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane)
have a disproportionate number of psychoactive genera with various indigenous
groups using geographically disparate members of these plant families for the same
psychoactive effect, an example of cultural convergence. Pharmacological traits related
to hallucinogenic and sedative potential are phylogenetically conserved within fam-
ilies. Unrelated families that exert similar psychoactive effects also modulate similar
neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological
mechanisms for stimulant effects were varied even within families suggesting that
stimulant chemicals may be more evolutionarily labile than those associated with
hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may
also exist in phylogenetically unrelated lineages, suggesting convergent evolution or
differential gene regulation of a common metabolic pathway. Our study has shown
that phylogenetic analysis of traditionally used psychoactive plants suggests multiple
ethnobotanical origins and widespread human dependence on these plants, motivating
pharmacological investigation into their potential as modern therapeutics for various
neurological disorders.
Subjects Anthropology, Biodiversity, Evolutionary Studies, Neuroscience, Plant Science
Keywords Ethnopharmacology, Drug discovery, Traditional medicine, Evolutionary ethnob-
otany, Neuropsychopharmacology, Psychotropic
INTRODUCTION
Plants constantly evolve to produce various defensive secondary metabolites against
their equally adaptive predators (Polya, 2003;Wink, 2003;Wink, 2016). Some well-
known psychoactive compounds such as atropine, caffeine, cocaine, nicotine and
How to cite this article Alrashedy and Molina (2016), The ethnobotany of psychoactive plant use: a phylogenetic perspective . PeerJ
4:e2546; DOI 10.7717/peerj.2546
morphine are believed to have been products of this evolutionary arms race (Howe
& Jander, 2008;Fürstenberg-Hägg, Zagrobelny & Bak, 2013). Psychoactive, alternatively
psychotropic, substances act on the nervous system affecting mental processes and behavior
(Spinella, 2001;Rätsch, 2005). They include hallucinogens that distort reality,
sedatives/narcotics that induce sleep, calmative or anxiolytics, antidepressants, and
stimulants that wake the mind (Spinella, 2001;Rätsch, 2005;Van Wyk & Wink, 2014).
Interestingly, humans have exploited alternate uses for plants containing psychoactive
phytochemicals that have purportedly evolved to ward off plant predators. However, the
affinity of these phytochemicals within the hominid nervous system may also indicate some
kind of mutualistic co-evolution, with ancient humans seeking and perhaps cultivating
plant psychotropics to facilitate survival, by alleviating starvation, fatigue and pain
(Sullivan & Hagen, 2002).
Psychoactive compounds have specific molecular targets in the nervous system, and
interact in a particular way with neuronal receptors to produce various psychoactive
effects (Spinella, 2001;Polya, 2003). For instance, morphine in opium poppy (Papaver
somniferum, Papaveraceae) eliminates pain by binding to opioid receptors (Polya, 2003),
but simultaneously promotes sedation and euphoria, by disinhibiting dopamine-containing
neurons in the limbic system (Johnson & North, 1992). Dopamine is ultimately responsible
for feelings of elation and satisfaction, which occur after some rewarding act like sex or food
satiety. Addiction arises from wanting to re-experience the pleasure due to the drug’s ability
to cause dopamine buildup (Lüscher & Ungless, 2006). Compounds that mimic serotonin
and act as receptor agonists like mescaline in the peyote cactus (Lophophora williamsii,
Cactaceae), trigger hallucinations and cognitive breakdown (Polya, 2003). Stimulating
substances, such as the alkaloid nicotine in tobacco, Nicotiana tabacum (Solanaceae),
mimic the endogenous neurotransmitter acetylcholine stimulating muscle contractions
and cholinergic areas of the brain involved in arousal and attention (Polya, 2003). Yet, the
confamilial Atropa belladonna, contains a chemically different alkaloid, atropine, which
promotes sedation and incapacitation via its action as muscarinic acetylcholine antagonist,
blocking neuromuscular communication (Spinella, 2001).
It is well established that all cultures, ancient or modern, have some kind of drug culture,
relying on psychoactives for recreational, ritual and/or medicinal uses (Schultes, 1976;
Schultes, Hofmann & Rätsch, 2001;Rätsch, 2005). Shamanistic religions have existed in the
Old World of Europe, Asia and Africa, believing that psychoactive plants are capable of
healing through divine power. Marijuana (Cannabis spp., Cannabaceae) and opium poppy
are among the most popular psychoactive plants used by Old World shamans. Marijuana
was used in ancient China for various afflictions like malaria and constipation, and even
as a narcotic in surgeries. In India, the plant was considered sacred promoting pleasurable
sensations in the user (Clarke & Merlin, 2013). Tetrahydrocannabinol (THC) in marijuana,
exerts these actions by binding to cannabinoid receptors, mediating sensory pleasure
(Mahler, Smith & Berridge, 2007). Another familiar psychoactive, opium poppy was used
for medicinal and recreational purposes. It probably originated in the Mediterranean, but
widespread use has confounded its evolutionary origin (Merlin, 2003). It was recorded
in the Eber papyrus, an ancient Egyptian scroll, that opium poppy was used to stop the
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 2/30
excessive crying of children (Vetulani, 2001). The plant contains morphine and codeine
that are responsible for its hypnotic and analgesic properties (Heinrich et al., 2012).
Indigenous people of the New World have also used psychotropic substances,
including tobacco, ayahuasca, and coca, even more so than cultures of the Old World
(Schultes, 1976). Tobacco from the leaves of N. tabacum has long been used in the Americas,
with cultivation in pre-Columbian Mexico or Peru (Rätsch, 2005). American Indians
believed in the medicinal power of tobacco, and it was smoked in ceremonial peace pipes
to seal covenants. In the Amazon Basin of South America, the hallucinogenic beverage,
ayahuasca, is made by healers from the boiled crushed stems of the caapi, Banisteropsis
caapi (Malpighiaceae), along with the leaves of chacruna, Psychotria viridis (Rubiaceae).
Chacruna contains serotonergic N, N-dimethyltryptamine (DMT), that is activated by
the beta-carbolines in caapi (McKenna, 1996). In the Andes, indigenous peoples chew
coca leaves of Erythroxylum coca (Erythroxylaceae) to cope with hard labor, removing
symptoms of fatigue and hunger (Nigg & Seigler , 1992). Its cocaine content prevents
dopamine reuptake producing increased energy and mood elevation (Spinella, 2001).
The ubiquity of psychoactive plants in various cultures motivates investigation of the
commonalities among these plants, in which a phylogenetic framework may be insightful.
Information is assigned to nodes of the phylogeny, instead of one species at a time,
facilitating the study of trait distributions (Saslis-Lagoudakis et al., 2015). Phylogenetic
studies of culturally diverse medicinal plants have repeatedly shown that medicinal uses
and phytochemical traits are not randomly distributed on the phylogeny, but are shared
by closely related plants, regardless of these plants’ cultural and geographic designations
(Saslis-Lagoudakis et al., 2012;Saslis-Lagoudakis et al., 2015;Xavier & Molina, 2016). In
this study we aimed to understand if there is a similar pattern of cultural convergence
(Xavier & Molina, 2016) in psychoactive plants using phylogenetic analysis—does the
phylogeny of culturally important psychoactive plants reveal a preference for certain
plant families and for specific psychoactive effects (hallucinogenic, sedative, stimulant,
etc.)? Additionally, we sought to understand if there is also a pattern of mechanistic
convergence, such that unrelated plants with similar psychoactive effects ultimately affect
similar neurotransmitter systems. Our study provides insight into the ethnobotanical
origins of psychoactive plant use and suggests new plant sources of psychopharmacological
drugs.
MATERIALS AND METHODS
Pyschoactive taxa of seed plants (126 genera) used by various indigenous groups were
compiled for this study (Table 1), but plants with psychoactive uses only after alcoholic
fermentation were excluded (e.g., wine from grapes, Vitis vinifera). Congeneric species
were only represented once in the phylogeny, e.g., Datura spp. included D. discolor Bernh.,
D. ferox L., D. innoxia Mill., D. metel L., D. stramonium L., D. wrightii Regel. This is to
account for taxonomic uncertainties that are common in species circumscriptions, and
also not to visually bias the phylogeny towards a certain family with multi-species genera
(e.g., Datura). The plants’ names were verified in (The Plant List, 2013), a working list
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 3/30
Table 1 Psychoactive plant taxa in this study. Culturally diverse psychoactive plant taxa, their uses, indigenous psychoactive cultural origin, and corresponding
Genbank numbers.
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Acanthaceae
(Lamiales)
Justicia pectoralis Jacq. justicia Native American
(Rätsch, 2005)
Hallucinogen, antidepres-
sant, sedative, aphrodisiac
(Rätsch, 2005)
AJ879453
Acoraceae
(Acorales)
Acorus calamus L. sweet flag Indomalayan, Temperate Asian
(Rätsch, 2005)
Stimulant, antidepressant,
sedative (Rätsch, 2005)
AJ879453
Aizoaceae
(Caryophyl-
lales)
Sceletium spp. kougoed African and Middle Eastern
(Gericke & Viljoen, 2008)
Sedative, analgesic
(Gericke & Viljoen, 2008)
HM850175
Apiaceae
(Apiales)
Angelica sinensis (Oliv.)
Diels
dong quai Temperate Asian
(Rätsch, 2005)
Stimulant, sedative
(O’Mahony, 2010)
GQ436632
Apiaceae
(Apiales)
Centella asiatica (L)
Urb.
gotu kola Indomalayan, Temperate Asian
(Rätsch, 2005)
Antianxiety, antidepressant
(Mamedov, 2005)
GQ436635
Apocynaceae
(Gentianales)
Alstonia scholaris (L.)
R. Br.
dita African and Middle Eastern,
Australasian, Indomalayan
(Rätsch, 2005;Arulmozhi et al.,
2012)
Stimulant, antianxiety, an-
tidepressant, sedative, anal-
gesic, aphrodisiac (Rätsch,
2005;Arulmozhi et al., 2012)
EU916739
Apocynaceae
(Gentianales)
Apocynum venetum L luobuma Temperate Asian
(Grundmann et al., 2007)
Antianxiety, antidepressant
(Grundmann et al., 2007;
Zheng, Fan & Liu, 2013)
KP088474
Apocynaceae
(Gentianales)
Carissa edulis (Forssk.)
Vahl
Arabian
numnum
African and Middle
Eastern (Rätsch, 2005)
Hallucinogen, aphrodisiac
(Rätsch, 2005)
JF265327
Apocynaceae
(Gentianales)
Rauvolfia
serpentina (L.)
Benth. ex Kurz
snakeroot Indomalayan
(Mamedov, 2005)
Antianxiety, antidepres-
sant, sedative, analgesic
(Spinella, 2001;Mamedov,
2005;Rätsch, 2005)
KJ667614
Apocynaceae
(Gentianales)
Tabernaemontana spp. milkweed Indomalayan, African,
Native American
(Rätsch, 2005)
Hallucinogen, stimulant,
antidepressant, sedative,
analgesic (Rätsch, 2005;
Pratchayasakul et al., 2008;
Cardoso et al., 2015)
EU916740
Apocynaceae
(Gentianales)
Tabernanthe iboga
Baill.
iboga African and Middle
Eastern (Sayin, 2014)
Hallucinogen, stimulant, an-
tianxiety, antidepressant,
analgesic, aphrodisiac (Nigg
& Seigler, 1992;Sayin, 2014)
AJ419763
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 4/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Apocynaceae
(Gentianales)
Voacanga spp. voacango
bush
African and Middle
Eastern (Rätsch, 2005)
Hallucinogen, stimulant,
aphrodisiac (Rätsch, 2005)
KC628529
Aquifoliaceae
(Aquifoliales)
Ilex spp. yerba
mate
Native American
(Rätsch, 2005)
Stimulant (Rätsch, 2005)FJ394625
Araliaceae
(Apiales)
Panax ginseng
C.A.Mey.
ginseng Temperate Asian
(Rätsch, 2005)
Stimulant, antidepressant,
aphrodisiac (Rätsch, 2005)
KM088019
Arecaceae
(Arecales)
Areca catechu L. betel nut Indomalayan
(Rätsch, 2005)
Stimulant, sedative, aphro-
disiac (Rätsch, 2005)
JX571781
Asteraceae
(Asterales)
Artemisia spp. wormwood European; Temperate Asian
(Rätsch, 2005;Sayin, 2014)
Hallucinogen, stimulant,
analgesic aphrodisiac
(Rätsch, 2005;Sayin, 2014)
KM360653
Asteraceae
(Asterales)
Calea ternifolia Oliv dream
herb
Native American
(Rätsch, 2005)
Hallucinogen, sedative
(Rätsch, 2005)
AY215089
Asteraceae
(Asterales)
Lactuca virosa Habl. wild
lettuce
African and Middle
Eastern (Rätsch, 2005)
Sedative, aphrodisiac
(Rätsch, 2005)
KM360888
Asteraceae
(Asterales)
Tagetes spp. Mexican
marigold
Native American
(Rätsch, 2005)
Hallucinogen,
stimulant, antianxiety,
antidepressant, aphrodisiac
(Rätsch, 2005)
AY215184
Bignoniaceae
(Lamiales)
Bignonia nocturna
(Barb.Rodr.)
L.G.Lohmann
[=Tanaecium
nocturnum
(Barb.Rodr.) Burea &
K.Schum.]
koribo Native American
(Rätsch, 2005)
Sedative, analgesic
and aphrodisiac
(Rätsch, 2005)
KR534325
Burseraceae
(Sapindales)
Boswellia sacra Flueck. olibanum
tree
African and Middle
Eastern (Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
KT934315
Cactaceae
(Caryophyl-
lales)
Ariocarpus fissuratus
(Engelm.) K.Schum.
chautle Native American
(Rätsch, 2005)
Hallucinoge, analgesic
(Rätsch, 2005)
KC777009
Cactaceae
(Caryophyl-
lales)
Echinopsis spp. (incl.
Trichocereus pachanoi
Britton & Rose)
San Pedro
cactus
Native American
(Rätsch, 2005)
Hallucinogen, stimulant
(Rätsch, 2005)
FR853367
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 5/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Cactaceae
(Caryophyl-
lales)
Lophophora williamsii
(Lem. Ex Salm-Dyck)
J.M. Coult.
peyote Native American
(Vetulani, 2001)
Hallucinogen
(Vetulani, 2001)
KC777011
Cactaceae
(Caryophyl-
lales)
Mammillaria spp. false
peyote
Native America
(Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
KC777008
Cactaceae
(Caryophyl-
lales)
Pachycereus pecten-
aboriginum (Engelm.
ex S. Watson) Britton
& Rose
pitayo Native American
(Schultes, 1976)
Hallucinogen
(Schultes, 1976)
JN191499
Campanulaceae
(Asterales)
Lobelia tupa L. tupa Native American
(Schultes, 1976)
Hallucinogen, sedative
(Schultes, 1976;Rätsch, 2005)
EF174606
Cannabaceae
(Rosales)
Cannabis spp. marijuana Indomalayan, Temperate Asian
(Rätsch, 2005)
Hallucinogen, stimulant, an-
tianxiety, antidepressant,
sedative, analgesic, aphro-
disiac (Rätsch, 2005)
AF500344
Cannabaceae
(Rosales)
Humulus lupulus L. hops European (Rätsch, 2005) Antianxiety, sedative (Hein-
rich et al., 2012)
KT266264
Caprifoliaceae
(Dipsacales)
Nardostachys jatamansi
(D. Don) DC.
jatamansi Indomalaya
(Chaudhary et al., 2015)
Antidepressant, sedative
(Chaudhary et al., 2015)
AF446950
Caprifoliaceae
(Dipsacales)
Valeriana officinalis L. valerian European
(Heinrich et al., 2012)
Antianxiety and sedative
(Heinrich et al., 2012)
AY362490
Celastraceae
(Calastrales)
Catha edulis (Vahl)
Endl.
khat African and Middle
Eastern (Rätsch, 2005)
Stimulant, antidepressant,
aphrodisiac (Rätsch, 2005)
JQ412336
Columelliaceae
(Bruniales)
Desfontainia spinosa
Ruiz & Pav.
taique Native American
(Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
Z29670
Combretaceae
(Myrtales)
Terminalia bellirica
(Gaertn.) Roxb.
bellerian
my-
robalan
Indomalaya
(Rätsch, 2005)
Hallucinogen, sedative
(Rätsch, 2005)
KT279740
Convolvulaceae
(Solanales)
Argyreia nervosa
(Burm. F.) Bojer
(=Argyreia speciosa (L.
f.) Sweet)
Hawaiian
baby
Native American
(Rätsch, 2005)
Hallucinogen, analgesic,
aphrodisiac (Rätsch, 2005;
Galani, Patel & Patel, 2010)
KF242477
Convolvulaceae
(Solanales)
Convolvulus tricolor L. dwart
morning
glory
European (Rätsch, 2005) Sedative, analgesic
(Rätsch, 2005)
L11683
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 6/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Convolvulaceae
(Solanales)
Ipomoea spp. morning
glory
Native American
(Rätsch, 2005)
Hallucinogen, stimulant,
aphrodisiac (Rätsch, 2005;
Meira et al., 2012)
KF242478
Convolvulaceae
(Solanales)
Turbina corymbosa (L.)
Raf.
ololiuqui
vine
Native American
(Rätsch, 2005)
Hallucinogen, analgesic
(Rätsch, 2005)
AY100966
Cupressaceae
(Pinales)
Juniperus recurva
Buch.-Ham. ex D. Don
Himalayan
weeping
juniper
Indomalayan, Temperate Asian
(Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
JQ512552
Ephedraceae
(Ephedrales)
Ephedra spp. ephedra Temperate Asian
(Heinrich et al., 2012)
Stimulant (Rätsch, 2005)AY056562
Ericaceae
(Ericales)
Ledum palustre L. wild rose-
mary
Temperate Asian
(Rätsch, 2005)
Hallucinogen, sedative,
analgesic (Rätsch, 2005)
AF419831
Ericaceae
(Ericales)
Rhododendron molle
G.Don.
yang zhi
zhu
Temperate Asian
(Mamedov, 2005)
Antidepressant
(Mamedov, 2005)
AF421101
Erythroxylaceae
(Malpighiales)
Erythroxylum spp. Coca Native American
(Rätsch, 2005)
Stimulant, antianxiety,
analgesic and aphrodisiac
(Rätsch, 2005)
AB925614
Fabaceae
(Fabales)
Acacia spp. wattle African/Middle Eastern
Australasian, Indomalayan,
Native American (Rätsch, 2005)
Hallucinogen, aphrodisiac
(Rätsch, 2005)
HM849736
Fabaceae
(Fabales)
Anadenanthera spp. vilca,
yopo
Native American
(Rätsch, 2005)
Hallucinogen and analgesic
(Schultes, 1976)
KJ082119
Fabaceae
(Fabales)
Astragalus spp. milk
vetch
Native America
(Rätsch, 2005)
Hallucinogen (Rätsch, 2005)KU666554
Fabaceae
(Fabales)
Calliandra anomala
(Kunth) J.F. Macbr.
cabellito Native American
(Rätsch, 2005)
Hallucinogen and analgesic
(Rätsch, 2005)
AM234255
Fabaceae
(Fabales)
Desmanthus illinoensis
(Michx.) MacMill.
prairie
bundle
flower
Native American
(Halpern, 2004)
Hallucinogen (Halpern,
2004)
KP126868
Fabaceae
(Fabales)
Erythrina spp. coral trees Native American, Indomalaya
(Rätsch, 2005).
Hallucinogen and sedative
(Rätsch, 2005)
AB045801
Fabaceae
(Fabales)
Lonchocarpus violaceus
Benth.
balche’
tree
Native American
(Rätsch, 2005)
Hallucinogen (Rätsch, 2005)JQ626245
Fabaceae
(Fabales)
Mimosa spp. mimosa Native American, Indomalayan
(Rätsch, 2005)
Hallucinogenic, sedative,
aphrodisiac (Rätsch, 2005)
KJ773686
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 7/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Fabaceae
(Fabales)
Mucuna pruriens (L.)
DC.
velvet
bean
Indomalayan
(Lampariello et al., 2012)
Hallucinogen, aphrodisiac
(O’Mahony, 2010;
Lampariello et al., 2012)
EU128734
Fabaceae
(Fabales)
Rhynchosia pyramidalis
(Lam.) Urb.
bird’s
eyes
Native American
(Rätsch, 2005)
Sedative (Rätsch, 2005)KJ594450
Fabaceae
(Fabales)
Sophora secundiflora
(Ortega) DC.
mescal
bean
Native American
(Schultes, 1976)
Hallucinogen (Schultes,
1976)
Z70141
Hypericaceae
(Malpighiales)
Hypericum
perforatum L.
St. John’s
wort
European (Spinella, 2001) Antianxiety, antidepressant
(Spinella, 2001;
Heinrich et al., 2012)
AF206779
Iridaceae
(Asparagales)
Crocus sativus L. saffron European (Rätsch, 2005) Antianxiety, sedative, aphro-
disiac (Rätsch, 2005;Hossein-
zadeh & Noraei, 2009)
KF886671
Lamiaceae
(Lamiales)
Lavandula angustifolia
Mill. (=Lavandula of-
ficinalis Chaix)
lavender European (Rätsch, 2005) Antianxiety, sedative, anal-
gesic (Lis-Balchin & Hart,
1999;Hajhashemi, Ghannadi
& Sharif, 2003)
KT948988
Lamiaceae
(Lamiales)
Leonotis leonurus (L.)
R. Br.
lion’s tail African and Middle Eastern
(Rätsch, 2005)
Hallucinogen, sedative,
analgesic (Rätsch, 2005)
AM234998
Lamiaceae
(Lamiales)
Leonurus cardiaca L. motherwort European
(Rauwald et al., 2015)
Antianxiety, antidepres-
sant, sedative (Rauwald et al.,
2015)
KM360848
Lamiaceae
(Lamiales)
Melissa officinalis L. lemon
balm
European
(Vogl et al., 2013)
Antianxiety, sedative (Hein-
rich et al., 2012)
KM360879
Lamiaceae
(Lamiales)
Plectranthus
scutellarioides (L.)
R.Br. (=Coleus blumei
Benth.)
coleus Indomalayan
(Rätsch, 2005)
Hallucinogen, analgesic
(Rätsch, 2005)
JQ933273
Lamiaceae
(Lamiales)
Rosmarinus officinalis
L.
rosemary European
(Ferlemi et al., 2015)
Antianxiety,
antidepressant, analgesic
(Ferlemi et al., 2015)
KR232566
Lamiaceae
(Lamiales)
Salvia divinorum
Epling & Jativa
yerba de
la pastora
Native American
(Rätsch, 2005)
Hallucinogen, analgesic
(Rätsch, 2005)
AY570410
Lamiaceae
(Lamiales)
Scutellaria lateriflora L. skullcap Native American
(Awad et al., 2003)
Antianxiety, sedative
(Awad et al., 2003)
HQ590266
Lauraceae
(Laurales)
Cinnamomum cam-
phora (L.) J. Presl
camphor Indomalayan, Temperate Asian
(Rätsch, 2005)
Stimulant, sedative
(Rätsch, 2005)
L12641
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 8/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Lauraceae
(Laurales)
Sassafras albidum
(Nutt.) Nees
sassafras Native American
(Rätsch, 2005)
Stimulant (Rätsch, 2005)AF206819
Loganiaceae
(Gentianales)
Strychnos nux-vomica
L.
strychnine
tree
Indomalaya
(Rätsch, 2005)
Stimulant, antianxiety, an-
tidepressant, aphrodisiac
(Rätsch, 2005)
L14410
Lythraceae
(Myrtales)
Heimia salicifolia
(Kunth) Link
sinicuiche Native American
(Rätsch, 2005)
Hallucinogen, sedative
(Rätsch, 2005)
AY905410
Malpighiaceae
(Malpighiales)
Banisteriopsis spp. ayahuasca Native American
(Sayin, 2014)
Hallucinogen
(Sayin, 2014)
HQ247440
Malpighiaceae
(Malpighiales)
Diplopterys cabrerana
(Cuatrec) B. Gates
chaliponga Native American
(Sayin, 2014)
Hallucinogen (O’Mahony,
2010)
HQ247482
Malvaceae
(Malvales)
Cola spp. kola nut Africa and Middle Eastern
(McClatchey et al., 2009)
Stimulant (McClatchey et al.,
2009)
AY082353
Malvaceae
(Malvales)
Sida acuta Burm.f. broomweed Native America
(Rätsch, 2005)
Stimulant (Rätsch, 2005)KJ773888
Malvaceae
(Malvales)
Theobroma spp. cacao Native American
(Rätsch, 2005)
Stimulant (Rätsch, 2005)JQ228389
Malvaceae
(Malvales)
Tilia spp. linden European (Rätsch, 2005) Antianxiety, sedative
(Rätsch, 2005)
KT894775
Melanthiaceae
(Liliales)
Veratrum album L. white
hellebore
European (Rätsch, 2005) Hallucinogen
(Rätsch, 2005)
KM242984
Myristicaceae
(Magnoliales)
Horsfieldia australiana
S. T. Blake
nutmeg Australasian
(Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
KF496315
Myristicaceae
(Magnoliales)
Myristica fragrans
Houtt.
nutmeg Australiasia, Indomalaya
(Rätsch, 2005)
Hallucinogen, stimulant,
sedative aprhodisiac (Rätsch,
2005)
AF206798
Myristicaceae
(Magnoliales)
Osteophloeum
platyspermum (Spruce
ex A.DC.) Warb.
huapa Native American
(Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
JQ625884
Myristicaceae
(Magnoliales)
Virola elongata
(Benth.) Warb.
epena Native American
(Rätsch, 2005)
Hallucinogen, stimulant
(Rätsch, 2005)
JQ626043
Myrtaceae
(Myrtales)
Psidium guajava L. guava African and Middl Eastern
(Rätsch, 2005)
Sedative, analgesic (Rätsch,
2005)
JQ025077
Nitrariaceae
(Sapindales)
Peganum harmala L. harmal African and Middle Eastern
(Sayin, 2014)
Hallucinogen, stimulant,
analgesic (Vetulani, 2001;
Farouk et al., 2008)
DQ267164
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 9/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Nymphaeaceae
(Nymphaeales)
Nuphar lutea (L.) Sm. yellow
water lily
European (Rätsch, 2005) Sedative (Rätsch, 2005)DQ182338
Nymphaeaceae
(Nymphaeales)
Nymphaea spp. water lily African and Middle Eastern
(Rätsch, 2005)
Sedative (Rätsch, 2005)GQ468660
Olacaceae
(Santalales)
Ptychopetalum ola-
coides Benth.
marapuama Native American
(Piato et al., 2008)
Stimulant, Antidepressant
(Piato et al., 2008)
FJ038139
Orchidaceae
(Asparagales)
Vanilla planifolia Jacks.
ex Andrews
vanilla Native America
(Rätsch, 2005)
Stimulant, sedative,
aphrodisiac (Rätsch, 2005;
O’Mahony, 2010)
KJ566306
Orobanchaceae
(Lamiales)
Cistanche deserticola
K.C.Ma
rou cong
rong
Temperate Asian
(Wang, Zhang & Xie, 2012)
Stimulant, aphrodisiac
(O’Mahony, 2010)
KC128846
Pandanaceae
(Pandanales)
Pandanus spp. screwpine Australasian
(Rätsch, 2005)
Hallucinoge, analgesic
(Rätsch, 2005)
JX903247
Papaveraceae
(Ranuncu-
lales)
Argemone mexicana L. Mexican
poppy
Native American
(Rätsch, 2005)
Hallucinogen, sedative, anal-
gesic, aphrodisiac (Rätsch,
2005;Brahmachari, Gorai &
Roy, 2013)
U86621
Papaveraceae
(Ranuncu-
lales)
Eschscholzia californica
Cham.
California
poppy
Native American
(Rolland et al., 1991)
Antianxiety, sedative, anal-
gesic (Rolland et al., 1991)
KM360775
Papaveraceae
(Ranuncu-
lales)
Meconopsis horridula
Hook. f. & Thomson
prickly
blue
poppy
Temperate Asian
(Fan et al., 2015)
Sedative, analgesic (Fan et
al., 2015)
JX087717
Papaveraceae
(Ranuncu-
lales)
Papaver somniferum L. opium
poppy
African and Middle Eastern
(Vetulani, 2001)
Hallucinogen, sedative, anal-
gesic, aphrodisiac (Rätsch,
2005)
KU204905
Passifloraceae
(Malpighiales)
Passiflora spp. passion
flower
Native American
(Rätsch, 2005)
Antianxiety, sedative (Hein-
rich et al., 2012)
HQ900864
Passifloraceae
(Malpighiales)
Turnera diffusa Willd.
ex Schult.
damiana Native American
(Rätsch, 2005)
Stimulant, antianxiety,
aphrodisiac (Rätsch, 2005)
JQ593109
Phytolaccaceae
(Caryophyl-
lales)
Phytolacca acinosa
Roxb.
pokeweed Temperate Asian
(Rätsch, 2005)
Hallucinogen (Rätsch, 2005)HM850257
Piperaceae
(Piperales)
Arundo donax L. giant reed African and Middle
Eastern; Native American
(Rätsch, 2005)
Hallucinogen (Rätsch, 2005)U13226
Piperaceae
(Piperales)
Piper spp. pepper,
kava
Native American, Indomalayan,
Australasian (Rätsch, 2005)
Stimulant, antianxiety, seda-
tive, analgesic, aphrodisiac
(Rätsch, 2005)
AY032642
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 10/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Plantaginaceae
(Lamiales)
Bacopa monnieri (L.)
Wettst.
brahmi Indomalayan (Shinomol, Muralid-
hara & Bharath, 2011)
Antianxiety, aphrodisiac
(Shinomol, Muralidhara &
Bharath, 2011)
KJ773301
Poaceae (Po-
ales)
Lolium temulentum L. bearded
darnel
African and Middle Eastern
(Rätsch, 2005)
Hallucinogen
(Rätsch, 2005)
KM538829
Ranunculaceae
(Ranuncu-
lales)
Aconitum spp. monkshood European, Indomalayan,
Temperate Asian
(Rätsch, 2005)
Hallucinogen, analgesic,
aphrodisiac (Rätsch, 2005)
EU053898
Ranunculaceae
(Ranuncu-
lales)
Hydrastis canadensis L. goldenseal Native American
(Foster & Duke, 2000)
Stimulant, sedative, analgesic
(O’Mahony, 2010)
L75849
Rubiaceae
(Gentianales)
Catunaregam nilot-
ica (Stapf) Tirveng.
(=Randia nilotica
Stapf)
chibra Africa and Middle Eastern
(Danjuma et al., 2014)
Antianxiety, antidepressant
(Danjuma et al., 2014)
AJ286700
Rubiaceae
(Gentianales)
Coffea arabica L. coffee African and Middle Eastern
(Rätsch, 2005)
Stimulant (Rätsch, 2005)EF044213
Rubiaceae
(Gentianales)
Corynanthe spp. pamprama African and Middle Eastern
(Rätsch, 2005)
Stimulant and aphrodisiac
(Rätsch, 2005)
AJ346977
Rubiaceae
(Gentianales)
Mitragyna speciosa
(Korth.) Havil
kratom Indomalaya (Idayu et al., 2011;
Suhaimi et al., 2016)
Stimulant, analgesic, sedative
(Rätsch, 2005;Suhaimi et al.,
2016)
AJ346988
Rubiaceae
(Gentianales)
Pausinystalia johimbe
(K.Schum.) Pierre ex
Beille
yohimbe African and Middle Eastern
(Rätsch, 2005)
Hallucinogen, stimulant,
antidepressant, aphrodisiac
(Rätsch, 2005)
AJ346998
Rubiaceae
(Gentianales)
Psychotria spp. chacruna Native American
(Rätsch, 2005)
Hallucinogen, sedative, anal-
gesic (Rätsch, 2005)
KJ805654
Santalaceae
(Santalales)
Santalum murrayanum
C.A Gardner
sandalwood Australasian
(Rätsch, 2005)
Sedative (Rätsch, 2005)L26077
Sapindaceae
(Sapindales)
Paullinia spp. guarana Native American
(McClatchey et al., 2009)
Stimulant (McClatchey et al.,
2009)
AY724365
Solanaceae
(Solanales)
Atropa belladonna L. belladonna European (Schultes, 1976) Hallucinogen, stimulant,
sedative, aphrodisiac (Rätsch,
2005)
AJ316582
Solanaceae
(Solanales)
Brugmansia spp. angel’s
trumpet
Native American
(Rätsch, 2005)
Hallucinogen, sedative,
aphrodisiac (Rätsch, 2005)
HM849829
(continued on next page)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 11/30
Table 1 (continued)
Family
(Order)
Accepted
binomial name
Common
name
Indigenous psychoactive culture Mechanism of action Genbank
numbers
Solanaceae
(Solanales)
Brunfelsia spp. raintree Native American
(Rätsch, 2005)
Hallucinogen, analgesic
(Rätsch, 2005)
AY206720
Solanaceae
(Solanales)
Cestrum spp. flowering
jessamine
Native American
(Rätsch, 2005)
Hallucinogen, sedative, anal-
gesic (Rätsch, 2005)
JX572398
Solanaceae
(Solanales)
Datura spp. toloache Native American, Indomalayan,
European (Rätsch, 2005)
Hallucinogen, sedative, anal-
gesic, aphrodisiac (Rätsch,
2005)
JX996059
Solanaceae
(Solanales)
Duboisia spp. pituri Australasian
(Rätsch, 2005)
Hallucinogen, stimulant,
aphrodisiac (Rätsch, 2005)
KM895868
Solanaceae
(Solanales)
Hyoscyamus spp. Henbane European (Rätsch, 2005) Hallucinogen. sedative
(Rätsch, 2005)
KF248009
Solanaceae
(Solanales)
Iochroma fuchsioides
(Bonpl.) Miers
yas Native American
(Rätsch, 2005)
Sedative (Rätsch, 2005)KU310432
Solanaceae
(Solanales)
Mandragora spp. mandrake European, African and
Middle Eastern (Rätsch, 2005;
Sayin, 2014)
Hallucinogen, sedative,
analgesic, aphrodisiac
(Rätsch, 2005;
Sayin, 2014)
U08614
Solanaceae
(Solanales)
Nicotiana spp. tobacco Native American, Australasian
(Vetulani, 2001;Rätsch, 2005)
Stimulant, antianxiety
(Rätsch, 2005)
KU199713
Solanaceae
(Solanales)
Petunia violacea Lindl. shanin Native American
(Schultes, 1976)
Hallucinogen (Schultes,
1976)
HQ384915
Solanaceae
(Solanales)
Physalis spp. groundcherry Native American
(Rätsch, 2005)
Sedative, analgesic (Rätsch,
2005)
KP295964
Solanaceae
(Solanales)
Scopolia carniolica Jacq. scopolia European (Rätsch, 2005) Hallucinogen, sedative,
aphrodisiac (Rätsch, 2005)
HQ216145
Solanaceae
(Solanales)
Solandra spp. arbol del
viento
Native American
(Knab, 1977;Rätsch, 2005)
Hallucinogen, aphrodisiac
(Knab, 1977;Rätsch, 2005)
U08620
Solanaceae
(Solanales)
Solanum spp. nightshade European, Native American
(Rätsch, 2005)
Sedative, analgesic (Rätsch,
2005)
KC535803
Solanaceae
(Solanales)
Withania somnifera
(L.) Dunal
ashwagandha Indomalayan (Rätsch, 2005) Sedative, aphrodisiac
(Rätsch, 2005)
FJ914179
Theaceae
(Ericales)
Camellia sinensis (L.)
Kuntze
tea Temperate Asian
(Rätsch, 2005)
Stimulant, aphrodisiac
(Rätsch, 2005)
EU053898
Urticaceae
(Rosales)
Urtica urens L. nettle African and Middle Eastern
(Doukkali et al., 2015)
Hallucinogen, antianxiety,
sedative (O’Mahony, 2010;
Doukkali et al., 2015)
KM361027
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 12/30
of all known plant species that is maintained by the Royal Botanic Gardens and the
Missouri Botanical Garden. The psychoactive uses of each plant were categorized as
follows: hallucinogen, sedative (=narcotic/hynotic), stimulant, anxiolytic (=relaxant), and
antidepressant. As psychotropic plants may also exert analgesia and/or aphrodisiac effects,
these effects were determined for each plant in addition to their original psychoactive
use. Multiple effects based on literature were not uncommon. Thus, plants were assigned
multiple psychoactive attributes, if applicable. For congeneric taxa, uses for each species
were all noted.
The 126 psychoactive plant taxa were categorized according to the ethnic groups they
were associated with: Native American (including North, Central and South America, 49
genera), European (15), Temperate Asian (including China, Russia, 10), Middle Eastern
and African (19), Indomalayan (including India and Southeast Asia, 10), Australasia
(including Australia, New Guinea, New Zealand, Pacific Islands, 4). Taxa with traditional
psychoactive uses in at least two of these groups were designated multi-cultural (19).
The uses of the plants were based on the originating indigenous cultures. For example,
harmal, Peganum harmala (Nitrariaceae), is native in the Mediterranean (Europe), but it
was used as a stimulant in the Middle East and in Africa, so harmal was assigned to the
latter. Guava, Psidium guajava (Myrtaceae), is native to tropical America, but was only
used as psychoactive in Africa (Rätsch, 2005). Argyreia nervosa (=A. speciosa), though of
Indian origin, is considered multi-cultural here. It has been used in Ayurvedic medicine
as an analgesic and aphrodisiac (Galani, Patel & Patel, 2010), but Hawaiians (Australasia)
have been using it as alternative to marijuana (Rätsch, 2005). Cultural designations for each
plant were all noted, with overlapping origins, if applicable, indicated.
To construct the phylogeny, the sequence of rbcL (the gene that codes for the
photosynthetic enzyme rubisco; Clegg, 1993) for each psychoactive plant taxon was
obtained from the GenBank database (http://www.ncbi.nlm.nih.gov/genbank) using
BLASTN (e-value =0, query coverage >50%; Altschul et al., 1990). If there are multiple
species within the genus, only the genus name was indicated. The rbcL sequences were
not available in GenBank for the following species: Calea ternifolia, Calliandra anomala,
Crocus sativus, Horsfieldia australiana, Iochroma fuchsioides,Juniperus recurva, Justicia
pectoralis, Lactuca virosa, Ledum palustre, Lonchocarpus violaceus, Nymphaea ampla,
Pachycerus pectenaboriginum, Psychotria viridis, Ptychopetalum olacoides, Psidium guajava,
Rhynchosia pyramidalis, Sassafras albidum, Sceletium tortuosum, Tanaecium nocturnum,
Tilia tomentosa, Urtica urens, Veratrum album, and Virola elongata. In these cases, the rbcL
sequence for any species within the corresponding genus was downloaded instead.
The rbcL sequences of the psychoactive plants were aligned using default parameters
in MAFFT v.7 (Katoh & Standley, 2013). PhyML (Guindon & Gascuel, 2003) was utilized
to reconstruct the phylogeny applying the general time reversible (GTR) DNA model
(Tavaré, 1986) with aLRT (approximate likelihood ratio test) Shimodaira-Hasegawa-like
(SH-like) branch support (Simmons & Norton, 2014) and 100 bootstrap replicates. ITOL
(Interactive Tree of Life, http://itol.embl.de), a web-based tool used for the display and
manipulation of phylogenetic trees (Letunic & Bork, 2006), was used to highlight and map
the traits in Table 1 (indigenous culture, psychoactive uses). Affected neurotransmitter
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 13/30
(NT) systems (Table 2) for the main psychoactive families were also added to the phylogeny.
Cosmetic editing of the ITOL results was completed in Adobe Illustrator CS4.
RESULTS
The 126 psychoactive seed plant taxa belong to 56 families and 31 orders (Table 1) and
together comprise 1.6% of the total generic diversity for these families. The phylogeny
reflects expected relationships (The Angiosperm Phylogeny Group, 2016). Within eudicots
there seems to be cultural bias of psychotropic use toward asterid members (61) vs.
rosids (31). Nonetheless, the scattered distribution of psychoactive taxa throughout the
angiosperm phylogeny suggests that psychoactive phytochemicals have evolved multiple
times throughout angiosperm evolution. However, certain families are more diverse with
at least 3 or more genera: Myristicaceae, Papaveraceae, Malvaceae, Fabaceae, Cactaceae,
Asteraceae, Convolvulaceae, Solanaceae, Lamiaceae, Rubiaceae, Apocynaceae. However,
psychoactive diversity within these families may be positively correlated with the family’s
generic diversity. To test this, a Pearson’s product moment correlation coefficient was
calculated to test the relationship between the number of psychoactive genera in our study
versus the generic diversity of each family (from Christenhusz & Byng, 2016). Taxonomically
diverse families like Asteraceae and Rubiaceae (>500 genera each) did not always have
proportionally higher number of psychoactive genera with the correlation coefficient very
weakly positive (r=0.004). However, Myristicaceae (4 psychoactive genera out of 21 total),
Papaveraceae (4/42), Cactaceae (5/127), Convolvulaceae (4/53), Solanaceae (16/100),
Lamiaceae (8/241), Apocynaceae (7/366) have a disproportionate number (>1.6%) of
their family’s generic diversity psychoactive. We focused on the neurotransmitter systems
affected by psychotropic members of these families as well as psychoactive members in the
inherently diverse families of Fabaceae, Malvaceae, Rubiaceae, and Asteraceae (Fig. 1).
Unrelated families may exert similar psychoactive effects (Fig. 1). Cactaceae, Fabaceae,
Myristicaceae, Convolvulaceae, and Solanaceae are mainly hallucinogens, though they are
unrelated. Of the five cultural groups, Native Americans have traditionally used the most
psychoactives (49/126) with predilection for hallucinogens (Fig. 2) in Cactaceae, Fabaceae,
Convolvulaceae. These families mainly work as serotonin receptor agonists (Fig. 1;Table 2),
the same mechanism as hallucinogenic Myristicaceae that has been used in Australasia and
Indomalaya. Members of Solanaceae have also been used as hallucinogens, predominantly
by Native Americans and Europeans, but act via a different mechanism—as acetylcholine
antagonists. Hallucinogenic asterids are also often used as aphrodisiacs (16/30 =53% vs.
4/18 =22% hallucinogenic rosids).
The unrelated Papaveraceae and Lamiaceae similarly show sedative/narcotic qualities,
another popular psychoactive effect among different cultural groups (Fig. 2). However,
they affect different neurotransmitter systems with Papaveraceae working mainly as opioid
receptor agonists. Lamiaceae work as receptor agonists of gamma-amino butyric acid
(GABA), which also mediates the family’s anxiolytic effects. Psychoactive members of these
families also tend to exhibit analgesic effects.
Plants with anxiolytic and antidepressant properties are relatively sparse (Figs. 1 and 2),
with Europeans showing slightly increased use of these plants. Members of Apocynaceae
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 14/30
Table 2 Main psychoactive families (cf. Fig. 1), their primary psychoactive effect, suspected phytochemical constituents producing the effect, and the primary neu-
rotransmitter (NT) systems potentially affected. ‘‘±’’ refers to the activation (receptor agonist) and inhibition (receptor antagonist), respectively, of certain NT recep-
tors by the psychoactive substance.
Family Main
psychoactive
effect
Active phytochemicals Neurotransmitter systems affected
Apocynaceae Antidepressant Indole alkaloids, e.g., ibogaine, rauwolscine, reserpine,
yohimbine (Spinella, 2001;Polya, 2003;Rätsch, 2005;
Pratchayasakul et al., 2008;Sayin, 2014;Cardoso et al., 2015)
Serotonin (+), dopamine (+),
noradrenaline (+) (Wells, Lopez &
Tanaka, 1999;Spinella, 2001;Polya, 2003;
Grundmann et al., 2007;Arulmozhi et al.,
2012;Zheng, Fan & Liu, 2013;Sayin, 2014;
Cardoso et al., 2015) (except reserpine but
other indole alkaloids may counteract its
effects (Polya, 2003)
Asteraceae Hallucinogen,
aphrodisiac
Sesquiterpene lactones (Rätsch, 2005;Sayin, 2014) Unknown mechanisms for
various sesquiterpene lactones
(Chadwick et al., 2013)
Cactaceae hallucinogen Phenethylamine alkaloids, e.g., hordenine, mescaline,
pectenine (Rätsch, 2005;Sayin, 2014)
Serotonin (+) (Polya, 2003)
Convolvulaceae hallucinogen Ergot indole alkaloids (Rätsch, 2005;McClatchey et al.,
2009)
Serotonin (+) (Polya, 2003;Kennedy, 2014)
Fabaceae Hallucinogen Indole alkaloids, e.g., bufotenin, DMT; tryptamines
(Polya, 2003;Wink, 2003;Halpern, 2004;Rätsch, 2005)
Serotonin (+)
Lamiaceae Anxiolytic,
sedative,
analgesic
Terpenoids e.g., baicalin, linalool, labdane, rosmarinic
acid, salvinorin A, wogonin, etc. (Lis-Balchin & Hart,
1999;Awad et al., 2003;Awad et al., 2009;Polya, 2003;
Wink, 2003;Heinrich et al., 2012); leonurine alkaloid
(Rauwald et al., 2015)
GABA (+) (Awad et al., 2003;Awad et al.,
2009;Hajhashemi, Ghannadi & Sharif, 2003;
Shi et al., 2014;Rauwald et al., 2015)
Malvaceae Stimulant Xanthine alkaloids, e.g., caffeine, theobromine (in Cola,
Theobroma; Rätsch, 2005;McClatchey et al., 2009);
phenethylamine ephedrine (in Sida; Prakash, Varma &
Ghosal, 1981)
Adenosine () by xanthine alkaloids
(Polya, 2003;McClatchey et al., 2009);
adrenaline (+) by ephedrine (Polya, 2003)
Myristicaceae Hallucinogen DMT (indole alkaloid in Virola); phenylpropene e.g.,
myristicin, elemicine, safrole (Polya, 2003;Rätsch, 2005)
Serotonin (+) (Spinella, 2001;Polya, 2003)
Papaveraceae Hallucinogen Isoquinoline alkaloids, e.g., codeine; morphine; reticuline;
thebaine (Polya, 2003;Heinrich et al., 2012;Fedurco et al.,
2015;Shang et al., 2015)
Opioid (+) (Rolland et al., 1991;Polya,
2003;Shang et al., 2015)
Rubiaceae Stimulant caffeine (xanthine alkaloid in Coffea;Polya, 2003); indole
alkaloids in others, e.g., corynanthine, mitragynine,
yohimbine (indole alkaloid; Polya, 2003;Rätsch, 2005;
Suhaimi et al., 2016)
Adenosine () by xanthine alkaloids (Polya,
2003;McClatchey et al., 2009); adrenaline
(+) and serotonin (+) by indole alkaloids
(Polya, 2003)
Solanaceae Hallucinogen,
sedative,
Tropane alkaloids, e.g., atropine, hyoscyamine,
scopolamine (Polya, 2003;Wink, 2003;Rätsch, 2005)
Acetylcholine () (Polya, 2003)
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 15/30
Scopolia carniolica
Areca catechu
Cola spp
Mimosa spp
Mucuna pruriens
Passiflora spp
Lolium temulentum
Bacopa monnieri
Brugmansia spp
Theobroma spp
Alstonia scholaris
Atropa belladonna
Osteophloeum platyspermum
Acorus calamus
Ilex spp
Vanilla planifolia
Voacanga spp
Pausinystalia johimbe
Crocus sativus
Humulus lupulus
Sceletium spp
Pachycereus pectenaboriginum
Desfontainia spinosa
Tabernaemontana spp
Solanum spp
Randia nilotica
Mitragyna speciosa
Phytolacca acinosa
Cinnamomum camphora
Ipomoea spp
Lophophora williamsii
Lobelia tupa
Ariocarpus fissuratus
Hyoscyamus spp
Tagetes spp
Panax ginseng
Calea ternifolia
Cistanche deserticola
Arundo donax
Valeriana officinalis
Mandragora spp
Leonurus cardiaca
Ephedra spp
Erythrina spp
Strychnos nux-vomica
Desmanthus illinoensis
Melissa officinalis
Tanaecium nocturnum
Lavandula officinalis
Turnera diffusa
Lactuca virosa
Nuphar lutea
Artemisia spp
Myristica fragrans
Solandra spp
Astragalus spp
Psychotria spp
Diplopterys cabrerana
Cestrum spp
Anadenanthera spp
Convolvulus tricolor
Piper spp
Pandanus spp
Camellia sinensis
Urtica urens
Sida acuta
Iochroma fuchsioides
Carissa edulis
Duboisia spp
Sophora secundiflora
Scutellaria lateriflora
Banisteriopsis spp
Lonchocarpus violaceus
Datura spp
Acacia spp
Rauvolfia serpentina
Erythroxylum spp
Withania somnifera
Rosmarinus officinalis
Petunia violacea
Nicotiana spp
Tabernanthe iboga
Sassafras albidum
Horsfieldia australiana
Nardostachys jatamansi
Virola spp
Veratrum album
Argyreia nervosa
Echinopsis spp
Rhododendron molle
Coffea arabica
Cannabis spp
Hypericum perforatum
Corynanthe spp
Salvia divinorum
Catha edulis
Turbina corymbosa
Coleus blumei
Calliandra anomala
Physalis spp
Leonotis leonurus
Ledum palustre
Justicia pectoralis
Apocynum venetum
Centella asiatica
Paullinia spp
Terminalia bellirica
Heimia salicifolia
Aconitum spp
Meconopsis horridula
Ptychopetalum olacoides
Tilia spp
Argemone mexicana
Hydrastis canadensis
Papaver spp
Boswellia sacra
Santalum album
Eschscholzia californica
Nymphaea spp
Peganum harmala
Psidium guajava
Angelica sinensis
Brunfelsia spp
Mammillaria spp
Rhynchosia pyramidalis
Juniperus recurva
ASTERIDS
ROSIDS
MONOCOTS
???
GABA
adenosine
noradrenaline
serotonin
O
H2N
HO
O
NH
O
HN
O
NH
O
HN
S
OH
opioid
serotonin
serotonin
serotonin
acetylcholine
serotonin
adenosine
dopamine
Myristicaceae
Papaveraceae
Malvaceae
Fabaceae
Cactaceae
Asteraceae
Convolvulaceae
Solanaceae
Lamiaceae
Rubiaceae
Apocynaceae
Ha Sm Ax Ad Sd Ag Ap
EUDICOTS
noradrenaline
noradrenaline
Figure 1 The phylogeny (cladogram) of traditionally used psychoactive plant taxa. The phylogeny con-
forms to expected groupings (APG IV, 2016). The 11 main plant families are highlighted (top to bottom):
Myristicaceae, Papaveraceae, Malvaceae, Fabaceae, Cactaceae, Asteraceae, Convolvulaceae, Solanaceae,
Lamiaceae, Rubiaceae, Apocynaceae. Grey circles next to their family names are proportional to total
generic diversity within the family with lowest count for Myristicaceae (21 genera), and highest with 1623
genera for Asteraceae (Christenhusz & Byng, 2016). Branches are coded according to the different cultures
(Native American: red solid line; Middle Eastern and African: orange dashed line; European: blue solid
line; Indomalayan: green dotted line; Temperate Asia: pink solid line, Australasia: yellow solid line; Multi-
cultural: grey solid line). Branches in bold represent bootstrap node support >50% and SH-like branch
support >0.9. Psychoactive uses were overlain next to taxon names in columns (Ha, hallucinogen; Sm,
stimulant; Ax, anxiolytic; Ad, antidepressant; Sd, sedative; Ag, analgesic; Ap, aphrodisiac; along with the
primary neurotransmitters affected by the phytochemical/s exerting the dominant psychoactive effect (de-
lineated with boxes; cf. Table 2). Shaded plant families with phytochemicals that activate certain neuro-
transmitter systems (e.g., receptor agonists) show the neurotransmitter/s involved with green (bright)
background; phytochemicals with inhibitory effects to the NT have red (dark) background. In Asteraceae,
neuropharmacology is unclear (???).
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 16/30
Australasian (4)
Temperate Asian (10)
Indomalayan (10)
European (15)
African/Middle Eastern (19)
Native American (49)
Multi-cultural (19)
0
5
10
15
20
25
30
35
Hallucinogen
Stimulant
Antidepressant
Sedative
Analgesic
Aphrodisiac
African/Middle-Eastern (19)
Figure 2 Cultural distribution of psychoactive applications. Psychoactive plants were categorized ac-
cording to cultural affiliation and psychoactive uses. Each row shows the distribution of psychoactive uses
for plants within a cultural group. Of the 126 psychoactive plant genera, more than half of the plants are
used as hallucinogens mostly by Native Americans. Plants with sedative/narcotic qualities are also com-
monly sought after. Plants with anxiolytic and antidepressant effects are the least popular among different
cultures.
and Rubiaceae that show an antidepressant effect facilitate this effect by increasing synaptic
levels of monoamine neurotransmitters (serotonin, dopamine, noradrenaline; Fig. 1 and
Table 2). In contrast, plants with stimulating effects are numerous and randomly distributed
throughout the phylogeny, exhibiting varying mechanisms of action (see Malvaceae and
Rubiaceae, Fig. 1 and Table 2).
DISCUSSION
The phylogenetic distribution of psychoactive plants shows multiple evolutionary origins
and provides evidence for the adaptive benefit of phytochemicals that are psychoactive
in animals. It has been hypothesized that mammals may have sought plants with
these phytochemicals that were chemically similar to endogenous neurotransmitters
to augment their nutrition, as well as to facilitate survival, alleviating pain and hunger
(Sullivan & Hagen, 2002). Whether this phylogenetic distribution, showing multiple
independent origins of psychoactive plants, is due to co-evolutionary mutualism with
animals remains to be tested. However, it is clear that certain psychoactive effects are
concentrated in certain groups, which demonstrates that psychoactive phytochemicals
are phylogenetically clustered. Phylogenetic clustering of certain secondary metabolites
(Wink, 2003;Wink et al., 2010;Wink, 2013) and of medicinal traits (Saslis-Lagoudakis et
al., 2012;Saslis-Lagoudakis et al., 2015;Xavier & Molina, 2016) have also been revealed in
other studies.
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 17/30
In the phylogeny, 11 of 56 plant families have more psychoactive genera (three or
more) compared to others. Accounting for these families’ total generic diversity shows
that Myristicaceae, Papaveraceae, Cactaceae, Convolvulaceae, Solanaceae, Lamiaceae, and
Apocynaceae have a disproportionate number of psychoactive genera. The psychoactive
diversity of the other families, Fabaceae, Malvaceae, Asteraceae, and Rubiaceae, may be an
artifact of their overall higher generic diversity. Nonetheless, we see a pattern where these
plant families are being used for similar psychoactive applications by different cultures, a
pattern of cultural convergence (Xavier & Molina, 2016) with bias, interestingly, for plants
with hallucinogenic and sedative/narcotic potential.
Pharmacology of hallucinogenic plants
The use of hallucinogens is widespread in cultures which assigned positive meaning
to the experienced altered state of consciousness, such as allowing the user access to
the spiritual world (Júnior et al., 2015). Hallucinogens used in divination and religious
healing (i.e., entheogens) may have played a significant role in human evolution
(Schultes, Hofmann & Rätsch, 2001). Native Americans prolifically used hallucinogens,
but hallucinogenic use seems to be lower in temperate Asia. Increased hallucinogenic
use among indigenous peoples of Brazil (South America) was also reported by
Rodrigues & Carlini (2006).
In our study we find hallucinogenic plants in Myristicaceae, Fabaceae, Cactaceae,
and Convolvulaceae mainly acting as serotonin receptor agonists, a case of mechanistic
convergence where unrelated families exert the same psychoactive effect by affecting
identical neurotransmitter systems. Mescaline is the serotonergic chemical in Cactaceae,
while DMT (N,N-dimethyltryptamine) and bufotenin (Polya, 2003) have the same effect
and evolved independently in hallucinogenic taxa in Fabaceae (Wink, 2013). Serotonin
itself occurs in fabaceous Mucuna pruriens (Polya, 2003), a hallucinogen and aphrodisiac
in Ayurvedic medicine (Lampariello et al., 2012). DMT also exists in Virola of the unrelated
Myristicaceae (Polya, 2003), and the alkaloid, elemicine, in confamilial Myristica fragrans
transforms into a mescaline-like molecule (Rätsch, 2005).
The unrelated Convolvulaceae exerts hallucinogenic effects possibly through its ergot
alkaloids that work also as serotonin receptor agonists (Polya, 2003;Kennedy, 2014).
Yet interestingly, these ergot alkaloids originate from ascomycetous symbiotic fungi
(Beaulieu et al., 2013). Though endophytic fungi can produce some active metabolites
originally attributed to plants (Wink, 2008;Wink et al., 2010;Nicoletti & Fiorentino, 2015),
which may confound interpretation of the phylogeny, this was not the case, so far, for the
other main psychoactive families in our study. On the other hand, hallucinogenic taxa in
the closely related Solanaceae work on a different mechanism. Its tropane alkaloids such as
scopolamine and atropine act as muscarinic receptor antagonists, inhibiting acetylcholine
transmission (Spinella, 2001). Interestingly, in another asterid member, Salvia divinorum
(Lamiaceae), the diterpene, salvinorin A, possibly works as a hallucinogen through its action
on specific opioid receptors (kappa) (Willmore-Fordham et al., 2007), the same receptor
modulated by the alkaloid ibogaine in hallucinogenic Tabernanthe iboga (Apocynaceae;
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 18/30
Spinella, 2001). Various unrelated taxa seemingly achieve their hallucinogenic effects by
modulating serotonin, acetylcholine, and/or endogenous opioids.
It is interesting that in many hallucinogenic asterids, aphrodisiac effects are quite
common (see Asteraceae, Solanaceae, Apocynaceae). In members of Solanaceae this effect
may be due to dopamine increase from cholinergic antagonism (Spinella, 2001). Dopamine
is important in sexual arousal and orgasm (Krüger, Hartmann & Schedlowski, 2005).
This neurotransmitter is also modulated by ibogaine in T. iboga (Wells, Lopez & Tanaka,
1999), which is also traditionally used as an aphrodisiac along with other Apocynaceae
members. In another asterid family, Asteraceae, it is not clear which of its phytochemical
constituents produce psychoactive effects, except perhaps for wormwood (Artemisia spp.)
wherein the monoterpenoid, thujone, antagonizes the main inhibitory neurotransmitter,
gamma-aminobutyric acid (GABA), resulting in its stimulant, almost convulsant, effects
(Höld et al., 2000). However, the great diversity of sesquiterpene lactones prevalent in the
family (Chadwick et al., 2013) are likely implicated in its hallucinogenic and aphrodisiac
potential (Fig. 1 and Table 2). These findings motivate further research into these asterid
families as new therapeutics for sexual dysfunction.
Pharmacology of plants with sedative and analgesic effects
Dr. WE Dixon, well-known British pharmacologist of his time, once commented that
narcotic indulgences reflect the sad paradox that humans seemed to get their ‘‘chief
pleasures in life by escaping out of life’’ (Narcotic Plants, 1928: 252). There may be truth
to this as narcotic/sedative effects were commonly sought for by various cultures, second
to hallucinogens, with members of Papaveraceae and Lamiaceae traditionally used for
this purpose. Opium poppy of Papaveraceae has long been known to ancient Greeks and
Sumerians and is considered one of the most important medicinal plants in history. Its
opium latex is the source of >30 alkaloids including morphine and codeine, which bind to
opioid receptors, promoting sedation and analgesia (Heinrich et al., 2012). Though there
are other members of Papaveraceae that have been used by Asians and Native Americans
for sedation and pain relief (Rolland et al., 1991;Brahmachari, Gorai & Roy, 2013;
Shang et al., 2015), the substances responsible for their effects are not well characterized as
in opium poppy, but it is possible that their effects are also mediated via opioid receptors
(Shang et al., 2015) and at least in Eschscholzia californica (California poppy) via the
GABAergic system (Fedurco et al., 2015).
In asterids, sedation is produced by members of Solanaceae and Lamiaceae possibly
via different pathways. Tropane alkaloids in Solanaceae (Wink, 2003), particularly
scopolamine, promote sedation through depression of the central nervous system
resulting from anticholinergic activity (Renner, Oertel & Kirch, 2005). In Lamiaceae, this
effect is mainly facilitated via the GABAergic pathway (Shi et al., 2014), with leonurine
(Rauwald et al., 2015) and essential oil components (Lisbalchin & Hart, 1999;Wink,
2003;Awad et al., 2009;Shi et al., 2014;Ferlemi et al., 2015) as the primary chemicals
that increase GABA. Coincidentally, Lamiaceae members also possess analgesic effects,
but the pharmacology is unclear (Hajhashemi, Ghannadi & Sharif, 2003;Dobetsberger &
Buchbauer, 2011) and may reflect the antinociceptive properties of activation of GABA
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 19/30
receptors (Enna & McCarson, 2006). Salvia divinorum however, does not contain essential
oils (Rätsch, 2005), but has been pharmacologically shown to exert analgesic quality through
activation of the same opioid receptors (kappa) implicated in its hallucinogenic effect
(Willmore-Fordham et al., 2007), a mechanism different from the other Lamiaceae species
here. Some members of the distantly related Rubiaceae, including Psychotria colorata
(Elisabetsky et al., 1995) and Mitragyna speciosa (Suhaimi et al., 2016), have also shown
similar opiate-like antinociceptive properties, confirming their traditional uses. Repeated
evolution of phytochemicals with affinity for animal opioid receptors may imply some
adaptive benefit to plants.
Pharmacology of plants with anxiolytic and antidepressant effects
The relatively sparse distribution of anxiolytic and antidepressant plants in the phylogeny
compared to hallucinogens and sedatives, suggests that there is less cultural utility for plants
with these psychoactive properties. In the US there is a cultural aspect to the pathogenesis
of anxiety and depression with minority groups reporting lower incidence compared to
whites (Hofmann, Asnaani & Hinton, 2010). The definition itself of depression is wrought
with Western assumptions of individual happiness, which is in contrast to other cultures’
view of happiness arising from social interdependence (Chentsova-Dutton, Ryder & Tsai,
2014). This may explain why these psychoactive uses were less prevalent compared to
hallucinogenic, stimulant and sedative applications.
Sedative members of Lamiaceae often possess anxiolytic qualities (Fig. 1), and this is
probably due to overlapping effects on GABA (Tallman et al., 2002). Phytol, an alcohol
in essential oils (Costa et al., 2014) has been shown to increase GABA. Rosmarinic acid in
rosemary (R. officinalis) and lemon balm (M. officinalis), both Lamiaceae, also works as
GABA transaminase inhibitor preventing GABA catabolism (Awad et al., 2009).
In members of Apocynaceae and Rubiaceae (Gentianales) that show anxiolytic
and antidepressant effects, another mechanism may be involved. Rauvolfia serpentina
(Apocynaceae) is used in Ayurvedic medicine to treat depression (Mamedov, 2005). In
Africa, the confamilial T. iboga is used as a stimulant to combat fatigue and hunger, but
may have potential in easing depressive symptoms (Nigg & Seigler , 1992). Pausinystalia
yohimbe (Rubiaceae) has stimulating effects on the nervous system and has been used to
increase libido by men in central Africa (Rätsch, 2005). The confamilial M.speciosa has also
been used as stimulant to counteract fatigue and increase endurance for work in Southeast
Asia (Idayu et al., 2011). The main chemical constituents of these closely related families are
indole alkaloids that generally increase synaptic levels of the monoamine neurotransmitters,
serotonin, dopamine and noradrenaline by various mechanisms including inhibition of
transport and reuptake (Wells, Lopez & Tanaka, 1999;Zheng, Fan & Liu, 2013;Kennedy,
2014). The unrelated but popular herbal antidepressant, St. John’s wort (Hypericum
perforatum, Hypericaceae; Spinella, 2001), as well as pharmaceutical antidepressants,
produces its effects (Feighner, 1999) via the same mechanism of reuptake inhibition.
Monoamine transport inhibitors may be rife in Apocynaceae (or Gentianales). In her
ethnopharmacological studies of plants from South Africa, Jäger (2015) also discovered
two other Apocynaceae species that exhibited high affinity to the serotonin transporter.
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 20/30
Interestingly, these plants were also being used by traditional healers to treat those who
were ‘‘being put down by the spirits.’’ A primary side effect of many conventional
antidepressants is sexual dysfunction (Higgins, Nash & Lynch, 2010), which seems to
contradict the aphrodisiac effect exhibited by T. iboga and P. yohimbe, in addition to their
antidepressant effects. This suggests that members of Gentianales may be exploited as novel
pharmaceuticals for depression without the known side effects of sexual dysfunction.
Pharmacology of plants with stimulating effects
Plants traditionally used as stimulants are numerous and scattered throughout the
phylogeny, indicating that stimulant phytochemicals have evolved multiple times
independently in different lineages and may confer some evolutionary benefit. A few
display paradoxical effects as both stimulating and sedating, such as marijuana (Block et al.,
1998) and M. speciosa (Rätsch, 2005), which may be attributed to dosage, idiosyncrasies, or
antagonistic phytochemicals.
Albeit belonging to diverse families, coffee (Coffea arabica, Rubiaceae), yerba mate
(Ilex paraguariensis, Aquifoliaceae), kola (Cola spp., Malvaceae), tea (Camellia sinensis,
Theaceae), and guarana (Paullinia cupana, Sapindaceae), all contain caffeine, a xanthine
alkaloid, which acts as a stimulant through antagonism of adenosine receptors, interfering
with the binding of the inhibitory endogenous adenosine (Rätsch, 2005). Yohimbe
(P. yohimbe), though confamilial with coffee, contains the indole alkaloid, yohimbine,
which binds to adrenergic and serotonin receptors (Polya, 2003), and is structurally and
mechanistically similar to other stimulant alkaloids found in diverse plant groups such as
ergot alkaloids in Convolvulaceae, ibogaine in T. iboga and Voacanga sp. (Apocynaceae),
and harmaline in Peganum harmala (Nitrariaceae) (Polya, 2003).
Within the same family, particularly Solanaceae, contrasting effects and mechanisms
may also be observed. Though many solanaceous members contain tropane alkaloids
that work as anticholinergic hallucinogens with incapacitating effects, tobacco exerts
stimulant activity through an opposite mechanism, with nicotine, a pyrrolidine alkaloid,
promoting acetylcholine transmission. However, tropane alkaloids are not unique to
Solanaceae. Cocaine, found in the unrelated E. coca (Erythroxylaceae), suggests that
chemically similar alkaloids may evolve in divergent lineages (i.e., convergent evolution) or
alternatively, certain metabolic pathways have been evolutionarily conserved throughout
plant evolution and differential gene regulation is responsible for the expression of this
pathway (Wink, 2003;Wink, 2008;Wink et al., 2010;Weng, 2014). These may account for
the presence of ephedrine in the gymnosperm Ephedra spp. (Ephedraceae; Polya, 2003)
and the unrelated angiosperms Sida acuta (Malvaceae; Prakash, Varma & Ghosal, 1981)
and Catha edulis (Celastraceae; Polya, 2003). Ephedrine, a phenethylamine that mimics
noradrenaline, stimulates the adrenergic receptor system, and thus the sympathetic nervous
system responsible for the ‘‘fight-and-flight’’ response (Polya, 2003;Rätsch, 2005).
It is notable that, even within the same family, the stimulant phytochemicals are
chemically diverse. This phylogenetic pattern may indicate that stimulant chemicals may
be more evolutionarily labile than hallucinogenic and sedative phytochemicals that seem
to be more phylogenetically conserved within the family. As to why this is begs further
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 21/30
inquiry, but hints at the evolutionary benefits of these chemically diverse plant psychoactive
compounds that have evolved multiple times among seed plants, possibly with multifarious
roles other than to function solely as allelochemicals.
CONCLUSION
Phylogenetic analysis has demonstrated multiple evolutionary origins of traditionally
used psychoactive plant groups. Whether this pattern is due to repeated co-evolutionary
mutualism with animals remains to be tested. Psychoactive diversity of some highlighted
families is probably due to the inherent elevated diversity in these families. However,
other plant families have a disproportionate number of psychoactive genera, and their
phytochemical and psychoactive traits show phylogenetic clustering, with different
cultures converging on geographically-disparate members of these families for similar
uses: Myristicaceae, Cactaceae, Convolvulaceae, and Solanaceae as hallucinogens;
Papaveraceae, Lamiaceae for analgesia and sedation; Apocynaceae for antidepressant effects.
In certain unrelated families with the same psychoactive effect, the same neurotransmitter
systems were also affected, i.e., mechanistic convergence. However, this was not the
case for plants with stimulant effects, where confamilial taxa possess chemically diverse
stimulant alkaloids, and chemically similar stimulant alkaloids exist in diverse lineages.
Endophytic fungi can also produce some active metabolites originally attributed to plants
(Wink, 2008;Wink et al., 2010;Nicoletti & Fiorentino, 2015), and this should be considered
when interpreting the phylogeny.
Though we may have missed other psychotropic taxa, our study still provides insight
into the ethnobotanical origins of psychoactive plant use. The addition of these missing
taxa may only serve to corroborate our conclusion of widespread human dependence
on psychoactive plants and highlight other important psychoactive families and their
pharmacology. The brain is perhaps the most complex domain of the human body
(Singer, 2007), and therefore brain disorders are complex pathologies themselves
(Margineanu, 2016). Ethnobotanical research on how various human cultures have
exploited herbal therapy through time to treat neurological afflictions will continue to
provide insight into the etiology of these diseases and the success of folkloric treatments. Yet,
the astounding diversity of plant-based medicines may be better appreciated within an evo-
lutionary context that can reveal phylogenetic patterns that may guide future drug discovery
(Saslis-Lagoudakis et al., 2012;Xavier & Molina, 2016). Though chemically similar
psychoactive chemicals may exist in phylogenetically unrelated lineages, suggesting
convergent evolution or differential gene regulation of common metabolic pathways
(Wink, 2003;Wink, 2008;Wink et al., 2010), the majority of traditionally used psychoactive
plants generally display phylogenetic conservatism in phytochemistry and pharmacology,
and may be explored as novel therapeutics for neurological disorders such as depression,
anxiety, pain, insomnia and sexual dysfunction, reinforcing the potential of plant
psychoactives as ‘‘springboards for psychotherapeutic drug discovery’’ (McKenna, 1996).
Alrashedy and Molina (2016), PeerJ, DOI 10.7717/peerj.2546 22/30
ACKNOWLEDGEMENTS
This research was conceived as part of NA’s MSc thesis, and we are grateful to the King
Abdullah scholarship program (of Saudi Arabia) for sponsoring NA. We also thank NA’s
family and Michael Purugganan for various forms of support. We also thank Joseph Morin
and Timothy Leslie for reviewing earlier drafts of this manuscript. We are equally grateful
to the reviewers for their constructive comments.
ADDITIONAL INFORMATION AND DECLARATIONS
Funding
The authors received no funding for this work.
Competing Interests
The authors declare there are no competing interests.
Author Contributions
Nashmiah Aid Alrashedy performed the experiments, analyzed the data, contributed
reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables,
reviewed drafts of the paper.
Jeanmaire Molina conceived and designed the experiments, performed the experiments,
analyzed the data, contributed reagents/materials/analysis tools, wrote the paper,
prepared figures and/or tables, reviewed drafts of the paper.
Data Availability
The following information was supplied regarding data availability:
The research in this article did not generate, collect or analyse any raw data or code.
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... As well as realizing that cultural, educational, financial, etc. factors influence individual desire and societal acceptance and towards seeking out sources of relief from these disorders [1], [5], [187], [209], [212], [255]- [261], [49], [262], [84], [97], [101], [114], [115], [137], [173]. Leading to increasing interest towards utilizing traditional systems of medicine to due to their ubiquitous, culturally sensitive, and locally respected nature [10], [25], [27], [209]. Organizations and governments seek to incorporate or have already incorporated traditional systems of medicine and seek to do so by validating the medicinal properties of the various medicinal plants used in them [25], [68], [264], [92], [98], [110], [125], [180], [187], [211], [263]. ...
... This is particularly true for areas that do not have equal access to healthcare (i.e. underdeveloped, secluded, impoverished regions) and are either unable to access or afford the drugs needed [1], [25], [126], [137], [151], [163], [175], [179], [181], [182], [211], [271], [27], [381], [382], [43], [63], [72], [87], [90], [97], [98]. The remaining 10-15% of the population rely on medicines and drugs derived from plants for a significant portion of their pharmaceuticals [17], [41], [216], [368], [383], [62], [95], [122], [131], [161], [190], [196], [197]. ...
... Liriodenine, anonaine and nornuciferine ↑ DA, ↑ HVA, ↑ 5-HT, and ↑ 5-HIAA; ↑ turnover of DA and ↑ turnover of 5-HT; Antidepressant-like effect via ↑ MAO [9], [11], [238], [291], [293], [46], [74], [83], [136], [144], [153], [183], [185] Apocynum venetum Serotonergic via (5-HT3, 5-HT2A, and 5-HT1A) receptors, noradrenergic via (α1 and α2) receptors, and dopaminergic via (D1 and D2) receptors. Regulates of HPA activity and ↓ rising levels of CORT, CRH, ACTH and CRH, ↑ NE, ↑ 5-HT, and ↑ DA in Hipp [21], [27], [416], [442], [452], [453], [36], [200], [309], [342], [354], [386], [401], [412] PAST [36], [37], [39], [40], [51], [74], [82], [83], [89], [8], [98], [106], [109], [122], [144], [164], [200], [288], [309], [354], [9], [385], [386], [412], [414], [416], [426], [438], [454], [455], [10], [11], [13], [24], [27], [29] Artemisia capillaris Mugwort China Chlorogenic acid Opioidergic pathway [13], [35], [456], [457], [38], [40], [43], [109], [137], [176], [188], [ [5], [6], [43], [51], [62], [83], [89], [94], [98], [103], [106], [109], [13], [123], [125], [136], [148], [150], [188], [200], [235], [276], [309], [29], [316], [354], [390], [412], [416], [431], [438], [30], [ [5], [6], [46], [56], [62], [65], [83], [89], [98], [142], [149], [158], [13], [164], [188], [200], [263], [276], [288], [354], [373], [375], [376], [14], [386], [390], [401], [402], [410], [411], [414], [416], [433], [435], [18], [437], [450], [454], [458], [459], [27], [36], [39], [40], [43] Benincasa hispida [6], [13], [439], [40], [56], [83], [98], [112], [164], [200], [431] Berberis aristata Indian barberry Temperate Himalaya Berberine berberine: acts via the larginine-NO-cGMP pathway as well as δ opioid receptors. NOS converts l-arginine to NO, which results in ↑ cGMP in neuronal cells. ...
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Mental illness has long been a part of human history; however, not as long as humans have been using plants for medicinal purposes. Medicinal plants are the source of over 50% of our medications today. Several countries integrate traditional systems of medicine (homeopathic medicine) with international systems of medicine. However, the presence of medicinal plants for anxiolytic and anti-depressant medications is sorely lacking. This is despite a 30-year gap between the last new medications for anxiety and depressive disorders and the availability of ketamine in 2019. Several gaps and lack of access to research regarding the potential benefits of using medicinal plants as anxiolytic and antidepressant solutions create even more difficulties for researchers. In addition to this, the cost of development associated with creating new medications within this field of medicine is incredibly resource and time-intensive. Despite this level of stagnation pharmaceutical companies are still hesitant to approach medicinal plants and phytochemicals as potential sources of pharmaceutical interest. A hesitancy that seems to be echoed by several nations despite the vast amounts of money lost due to symptoms caused by anxiety and depressive disorders. This paper takes an in-depth look at all the issues listed above and more, analyzing the merit of researching/using medicinal plants for anxiolytic and antidepressant purposes, in the past, present, and potentially the future.
... Many of these plants contain phytochemicals with psychoactive and pharmacological effects ranging from sedation, stimulation to euphoria and hallucinations (Sobiecki, 2002). Moreover, their effects lead to altering of perception, emotion and cognition, and change in consciousness (Alrashedy and Molina, 2016;Khan et al., 2018;Martins and Brijesh, 2018 depression while only nine were phytochemically characterised to identify phytochemicals with antidepressant-like effects. A total of 24 phytochemicals with antidepressant-like effects have been isolated and identified (Table 3). ...
... Several biological assays have been used to investigate the antidepressant-like effects of South African medicinal plants, including in vitro biological assays (Nielsen et al., 2004;Sandager et al., 2005;Neergaard et al., 2009;Harvey et al., 2011;Stafford et al., 2013) and in vivo assays conducted using rodent models of depression (Machado et al., 2007;Machado et al., 2009;El-Alfy et al., 2010;Ahmadpoor et al., 2019;Rabiei and Setorki, 2019). The mechanism of action of most psychoactive compounds involves endocrine modulation of specific molecules in the CNS, modification of multiple biological effects on reuptake and/or receptor binding of various monoamines and interacting with neuronal receptors (Saki et al., 2014;Alrashedy and Molina, 2016). Medicinal plants and their bioactive compounds producing antidepressant therapeutic effects via interaction with serotonergic systems (SERT), noradrenergic (NAT) and dopaminergic (DAT) receptors (Machado et al., 2007;Stafford et al., 2008). ...
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Globally, the search for safe and potent natural-based treatment for depression is receiving renewed interest given the numerous side-effects associated with many existing drugs. In South Africa, the use of plants to manage depression and related symptoms is fairly documented among different ethnic groups. In the current study, we reviewed existing ethnobotanical, ethnopharmacological and phytochemical studies on South African medicinal plants used to manage depression. Electronic databases were accessed for scientific literature that meets the inclusion criteria. Plants with ethnobotanical evidence were subjected to a further pharmacological review to establish the extent (if any) of their effectiveness as antidepressants. Critical assessment resulted in 20 eligible ethnobotanical records, which generated an inventory of 186 plants from 63 plant families. Due to the cultural differences observed in the definition of depression, or lack of definition in some cultures, most plants are reported to treat a wide range of atypical symptoms related to depression. Boophone disticha, Leonotis leonurus and Mentha longifolia were identified as the three most popular plants, with over eight mentions each from the ethnobotanical records. The dominant families were Asteraceae (24), Fabaceae (16), Amaryllidaceae (10), and Apocynaceae (10) which accounted for about 32% of the 186 plants. Only 27 (≈14.5%) of the plants have been screened for antidepressant activity using in vitro and in vivo models. Agapanthus campanulatus, Boophone disticha, Hypericum perforatum, Mondia whitei and Xysmalobium undulatum, represent the most studied plants. Phytochemical investigation on nine out of the 27 plants revealed 24 compounds with antidepressant-like effects. Some of these included buphanidrine and buphanamine which were isolated from the leaves of Boophone disticha, Δ9-tetrahydrocannabinol, cannabidiol and cannabichromene obtained from the buds of Cannabis sativa and carnosic acid, rosmarinic acid and salvigenin from Rosmarinus officinalis, A significant portion (≈85%) of 186 plants with ethnobotanical records still require pharmacological studies to assess their potential antidepressant-like effects. This review remains a valuable reference material that may guide future ethnobotanical surveys to ensure their robustness and validity as well as database to identify promising plants to screen for pharmacology efficacy.
... A ethnomedicinal plant list has been obtained through literatures search from Scopus, PubMed, ScienceDirect, and Google Scholar. Data extraction was performed according to Alrashedy and Molina study [9] with some modification: (1) plants used in remedies were excluded and (2) congeneric taxa were presented once to avoid visually bias (e.g., Artemisia afra, Artemisia annua, Artemisia brevifolia, and Artemisia gmelinii were presented as Artemisia spp.). ...
... Other studies showed that stimulant chemicals were quite scattered in the phylogenetic tree. [9] Hence, prospective chance using this approach still needs to be explored. ...
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Emergence of artemisinin resistance leads the people to discover the new candidate for antimalarial drug. Combinatorial phylogeny and ethnobotanical approach may be useful to minimize the expenditure and time in laboratory testing. Seven hundred and thirty-three ethnomedicinal plants were listed from literature search. Obtained 340 internal transcribed spacer (ITS) sequences of plant list which met criteria were retrieved from GenBank NCBI and analyzed by MUSCLE and maximum likelihood phylogenetic test to generate the phylogenetic tree. Interactive phylogenetic tree was generated by Interactive Tree of Life (ITOL, https://itol.embl.de) and showed strong clustered pattern on Asteraceae. Afterward, 16 species of Asteraceae were selected to investigate the antimalarial activity, phytochemical, and genetic diversity. The presence of phytochemical was determined by standard method. DNA fluorescence-based assay was performed to determine the antimalarial activity against 3D7 Plasmodium falciparum. IC50μg/mL was used to categorize antimalarial activity. On the other hand, ITS universal primer was used to amplify and sequence the obtained extracted DNA of tested plant by cetyltrimethylammonium bromide method. Phylogenetic analyses were performed by MAFFT and RAxML with automatic bootstrapping. ITOL and Adobe Illustrator were used to generate interactive phylogenetic tree. All species tested showed the presence of phenolics and flavonoids, whereas alkaloids and terpenoids were shown vary among tested extracts. Among 16 species tested, 1 species exhibited good-moderate (Sphaeranthus indicus, IC506.59 μg/mL), 4 weak (Artemisia chinensis, Artemisia vulgaris, Tridax procumbens, and Blumea balsamifera), and 3 very weak (Eupatorium capillifolium, Wedelia trilobata, and Vernonia cinerea). Generated phylogenetic tree by ITS data was able to separate the tested species into their tribal classification. In addition, new medicinal properties of A. chinensis were discovered. Combining phylogeny approach with ethnobotanical data is useful to narrow down the selection of antimalarial plants candidate.
... Further important mechanisms of action of psychedelics involve reduced thalamic filtering of interoceptive and exteroceptive 1 We focus on psilocybin mushrooms as likely candidates for early psychedelic consumption in our lineage for the reasons enumerated here and because they require no preparation whatsoever, being bioactive in their natural state. Psychedelic plants in general were also ubiquitous and, in some instances, readily available (though certain plants required further processing to extract psychoactive secondary compounds) (Rätsch, 2005;Wink and van Wyk, 2008;Pennacchio et al., 2010;Alrashedy and Molina, 2016). information, which sustains an increased information flow to particular areas of the cortex (Vollenweider and Preller, 2020); and sensory bottom-up overflow and relaxed high-level priors (e.g., models related to self or social identity) as formulated by the relaxed beliefs under psychedelics (REBUS) model (Carhart-Harris and Friston, 2019; for further contextualization see Noorani and Alderson-Day, 2020). ...
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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 psilocybincontaining 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 wellbeing 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.
... Ethnomedicinally nutmegs and wild nutmegs were used to treat the nervous disorder, menstrual complications, rheumatism, asthma, skin infection, as a stimulant, aphrodisiac, abortifacient, blood purifier, antitumor, antidiarrhoeal agents, and others (Khare, 2008;Latha et al., 2005). Bark decoction of Compsoneura and Iryanthera was used as a topical wash to clean wounds (Gottlieb, 1979), Virola elongata in rheumatism, joint tumors, toothache, colic, dyspepsia (Alrashedy & Molina, 2016;Gottlieb, 1979;Holmstedt et al., 1980;McKenna, 1984), Virola bicuhyba as brain stimulant (Oliveira et al., 2011;Schultes, 1988), Knema elegans, K. furfuracea to cure cancer, mouth sore, dysentery (Henkin et al., 2017;Murray, Faraoni, Castro, Alza, & Cavallaro, 2013;Phadungkit et al., 2010;Pinto & Kijjoa, 1990) and indole alkaloids (143-159) and others (160) ( Table 3 and Table S1). ...
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Prized medicinal spice true nutmeg is obtained from Myristica fragrans Houtt. Rest species of the family Myristicaceae are known as wild nutmegs. Nutmegs and wild nutmegs are a rich reservoir of bioactive molecules and used in traditional medicines of Europe, Asia, Africa, America against madness, convulsion, cancer, skin infection, malaria, diarrhea, rheumatism, asthma, cough, cold, as stimulant, tonics, and psychotomimetic agents. Nutmegs are cultivated around the tropics for high‐value commercial spice, used in global cuisine. A thorough literature survey of peer‐reviewed publications, scientific online databases, authentic webpages, and regulatory guidelines found major phytochemicals namely, terpenes, fatty acids, phenylpropanoids, alkanes, lignans, flavonoids, coumarins, and indole alkaloids. Scientific names, synonyms were verified with www.theplantlist.org. Pharmacological evaluation of extracts and isolated biomarkers showed cholinesterase inhibitory, anxiolytic, neuroprotective, anti‐inflammatory, immunomodulatory, antinociceptive, anticancer, antimicrobial, antiprotozoal, antidiabetic, antidiarrhoeal activities, and toxicity through in‐vitro, in‐vivo studies. Human clinical trials were very few. Most of the pharmacological studies were not conducted as per current guidelines of natural products to ensure repeatability, safety, and translational use in human therapeutics. Rigorous pharmacological evaluation and randomized double‐blind clinical trials are recommended to analyze the efficacy and therapeutic potential of nutmeg and wild nutmegs in anxiety, Alzheimer's disease, autism, schizophrenia, stroke, cancer, and others.
... The evolutionarily related species also showed more medicinal value than the isolated evolutionary species [22]. However, some studies showed that not all biochemicals are clustered phylogenetically (e.g., stimulant chemicals from many investigated psychoactive plants showed to be more scattered rather than hallucinogen and sedative chemicals) [23], which is lead the uncertain robustness using this approach hence require to be explored furtherly [19]. ...
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Ethnobotanical-directed bioprospecting has made a significant contribution to modern drug discoveries. However, merely relying on this approach may spend more expenditure, time-consuming, and lead exhaustive laboratory testing due to the tremendous data of medicinal plants used and the occurrence of placebo effect during traditional medical treatment. Combining the phylogeny approach with ethnobotanical bioprospecting may become new prospective tools to lead the plant-based drug discovery, including antimalaria. This study aimed to map the ethnomedicinal plants used by various indigenous cultures to investigate the clustered pattern of its antimalarial properties for future bioprospecting. The Internal Transcribed Spacer (ITS) region sequences of selected 280 medicinal plants taxa obtained from NCBI (National Center for Biotechnology Information) were aligned by MUSCLE multiple sequences alignments. They were further analyzed using the Maximum Likelihood Phylogenetic Test by MEGA X software to construct the phylogenetic tree. Our research revealed that the medicinal plant taxa for malaria treatment was clumped in several families, including Apocynaceae, Euphorbiaceae, Rubiaceae, Rutaceae, Fabaceae were strongly clumped along with plants used for fever in the Asteraceae family. Interestingly, our finding showed that these plants were clumped in the sub-family of antimalarial producing species, the Asteroidea. Furthermore, the strongly clumping pattern was also shown in the tribe Heliantheae alliance of this sub-family. This finding supports the predictive power of phylogeny for future bioprospecting to select the candidate taxa to lead the drug discovery.
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The use of plants with psychoactive properties by ancient communities has been confirmed in numerous archaeological studies conducted in almost every place on earth. Many tribes used their own characteristic psychoactive potions and, according to researchers, their use fostered the integration of the members of a given community, facilitated their existence in an occupied area and could be of significant importance for its survival. Around the psychoactive plants and toxic secretions of some species of fauna a conglomerate of myths, cults and the properties attributed to them has developed. Permanent traces of their presence remain in both non-material and material culture. The aim of this article is to present the representations of psychoactive substances in the beliefs of ancient communities, their occurrence in myths, rock or sepulchral art, and to discuss the reasons for their use during rituals. The article presents also the main causes of the diffusion of the use of psychoactive plants from the sacred to the profane sphere.
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Ethnopharmacological relevance The burden of disease caused by mental and neurological disorders is increasing globally, to a disproportionate degree in Latin America. In contrast to the many psychoactive plants with a use history in Mesoamerican cultures, the translation to the wider population of knowledge around numerous botanicals used contemporarily by indigenous Mesoamerican societies to treat psychological and neurological disorders did not receive the same attention. Material and methods We used the previously published Mesoamerican Medicinal Plant Database to extract species and associated botanical drugs used as treatments for illnesses associated with the nervous system by Mesoamerican cultures in Belize, Guatemala, and Mexico. With the critical use of published pharmacological literature, the cross-culturally most salient genera are systematically reviewed. Results From 2188 plant taxa contained in the database 1324 are used as treatments for illnesses associated with the nervous system. The ethnomedical data was critically confronted with the available biomedical literature for the 58 cross-culturally most salient genera. For a considerable proportion of the frequently used taxa, preclinical data are available, mostly validating ethnomedicinal uses. Conclusion This quantitative approach facilitates the prioritization of taxa for future pre-clinical, clinical and treatment outcome studies and gives patients, practitioners, and legislators a fundamental framework of evidence, on which to base decisions regarding phytomedicines.
Chapter
Central nervous system disorders such as anxiety, depression, and Alzheimer’s occur as a result of the imbalance of neurotransmitters such as acetylcholine (Ach), dopamine (DA), serotonin (5-HT), and/or γ-aminobutyric acid (GABA). Such disorders may lead to emotional changes as well as impaired cognitive functions. Plants have been the predominant source of medicines throughout the vast majority of human history and remain so today outside of industrialized societies. Many plants are known for their anxiolytic, antidepressant, and memory-enhancing properties. Moreover, phytoconstituents, particularly alkaloids, have proven effectiveness as psychoactive lead drugs. In this chapter, we will have an overview of the most important psychoactive, neuroprotective, and antidepressant plants and phytoconstituents with emphasis on their mechanism of action.
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Cannabis: Evolution and Ethnobotany is a comprehensive, interdisciplinary exploration of the natural origins and early evolution of this famous plant, highlighting its historic role in the development of human societies. Cannabis has long been prized for the strong and durable fiber in its stalks, its edible and oil-rich seeds, and the psychoactive and medicinal compounds produced by its female flowers. The culturally valuable and often irreplaceable goods derived from cannabis deeply influenced the commercial, medical, ritual, and religious practices of cultures throughout the ages, and human desire for these commodities directed the evolution of the plant toward its contemporary varieties. As interest in cannabis grows and public debate over its many uses rises, this book will help us understand why humanity continues to rely on this plant and adapts it to suit our needs.
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Book
This book was tbe result of a symposium beld at tbe American Cbernical Society meeting in Miami Beacb, Florida, September 10-15, 1989. The symposium was jointly sponsored by Tbe Society for Economfc Botany and tbe American Cbernical Society Food and Natural Product sub division. Tbere were five speakers. During tbe social sessions (mostly over drinks in abotel room), it became obvious tbat, regardless of tbe discipline, we were all speaking tbe same language. Yet, prior to tbe symposium, only a few of tbe participants knew one anotber. We decided to expand tbe symposium into a book. The book would, we boped, accomplish for otbers wbat we bad discovered in ourselves. That is, the field of Natural Products is broad, but similar in techniques and approach, ancient but modern, and bas been and continues to be extremely valuable to humankind. We wanted the book to serve as an introductory text for courses and as a reference work for the future. We also determined to include the structure of every chemical in the chapter where it was mentioned so the reader would not have to find the structure somewhere else or to try and deduce the structure from the chemical name. Little did we know what an undertaking these goals would be or the time this would take.
Chapter
Mental health problems are a severe burden on society and are often under-prioritized in the healthcare system. Traditional healers might be well poised to treat mental diseases as they address their psychological, spiritual and cultural aspects as well as using medicine. Plants are sources of compounds that interact with most of the known pharmacological targets in the brain. Such compounds inhibit enzymes such as cholinesterases, monoamine oxidases and β-secretase, bind to receptors and transporters like the GABA and NMDA receptors and the serotonin transporter, prevent fibrillation of amyloid β peptides to form plaques and tangles, and might even dissolve the plaques. A wealth of preclinical work has identified plant species and compounds that have an effect on the CNS, what is needed are more well-conducted clinical trials. Only then can we make recommendations for phytotherapeutical and general healthcare practice.
Chapter
The scientific literature has shown a strong relationship between hallucinogenic plants and medical efficacy. Despite evidence from previous studies, however, many issues have not been discussed clearly enough to enable the acceptance of this relationship. From an evolutionary perspective, this relationship between the hallucinogenic properties and medicinal uses of plants may suggest that the use of hallucinogens derived from experimentation with medicinal plants in our evolutionary past. In this chapter, we discuss the evidence suggesting the medicinal role of hallucinogens in different cultures and present research findings that reflect on the adaptive significance of the use of hallucinogens. In this sense, we provide certain ideas that can guide future investigations that seek to understand the role played by hallucinogenic compounds in human evolution.