The ethnobotany of psychoactive plant use: a 1 phylogenetic perspective (#11617) First submission Please read the Important notes below, and the Review guidance on the next page. When ready submit online. The manuscript starts on page 3. Important notes Editor and deadline Michael Wink / 10 Jul 2016 Files Please visit the overview page to download and review the files not included in this review pdf. Declarations No notable declarations are present For assistance email [email protected] Review 2 guidelines Please in full read before you begin How to review When ready submit your review online. The review form is divided into 5 sections. Please consider these when composing your review: 1. BASIC REPORTING 2. EXPERIMENTAL DESIGN 3. VALIDITY OF THE FINDINGS 4. General comments 5. Confidential notes to the editor You can also annotate this pdf and upload it as part of your review To finish, enter your editorial recommendation (accept, revise or reject) and submit. BASIC REPORTING EXPERIMENTAL DESIGN Clear, unambiguous, professional English Original primary research within Scope of language used throughout. the journal. Intro & background to show context. Research question well defined, relevant Literature well referenced & relevant. & meaningful. It is stated how research fills an identified knowledge gap. Structure conforms to PeerJ standard, discipline norm, or improved for clarity. Rigorous investigation performed to a high technical & ethical standard. Figures are relevant, high quality, well labelled & described. Methods described with sufficient detail & information to replicate. Raw data supplied (See PeerJ policy). VALIDITY OF THE FINDINGS Impact and novelty not assessed. Conclusion well stated, linked to original Negative/inconclusive results accepted. research question & limited to supporting Meaningful replication encouraged where results. rationale & benefit to literature is clearly Speculation is welcome, but should be stated. identified as such. Data is robust, statistically sound, & controlled. The above is the editorial criteria summary. To view in full visit https://peerj.com/about/editorial- criteria/ Manuscript to be reviewed The ethnobotany of psychoactive plant use: a phylogenetic perspective Nashmiah Alrashedy 1 , Jeanmaire Molina Corresp. 1 1 Department of Biology, Long Island University, Brooklyn, New York, United States Corresponding Author: Jeanmaire Molina Email address: [email protected] 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, and aphrodisiacs). 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 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, with unrelated families exerting similar psychoactive effects and affecting identical 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. Our study has shown that phylogenetic analyses of traditionally used psychoactive plants suggests multiple ethnobotanical origins and widespread human dependence on these plants for survival, motivating pharmacological investigation into their potential as modern therapeutics for various neurological disorders. PeerJ reviewing PDF | (2016:06:11617:0:0:CHECK 26 Jun 2016) Manuscript to be reviewed 1 The ethnobotany of psychoactive plant use: a phylogenetic perspective 2 3 Nashmiah Alrashedy and Jeanmaire Molina* 4 Department of Biology, Long Island University-Brooklyn, 1 University Plaza, Brooklyn, NY, 5 USA 11201 6 7 *corresponding author: [email protected] 8 9 Abstract 10 Psychoactive plants contain chemicals that presumably evolved as allelochemicals but 11 target certain neuronal receptors when consumed by humans, altering perception, emotion and 12 cognition. These plants have been used since ancient times as medicines and in the context of 13 religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, 14 sedatives, and aphrodisiacs). The ubiquity of psychoactive plants in various cultures motivates 15 investigation of the commonalities among these plants, in which a phylogenetic framework may 16 be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with 17 their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The 18 phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The 19 plant families Myristicaceae (e.g. nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), 20 Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae 21 (dogbane) have a disproportionate number of psychoactive genera with various indigenous 22 groups using geographically disparate members of these plant families for the same psychoactive 23 effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and 1 PeerJ reviewing PDF | (2016:06:11617:0:0:CHECK 26 Jun 2016) Manuscript to be reviewed 24 sedative potential are phylogenetically conserved within families. Unrelated families that exert 25 similar psychoactive effects also modulate similar neurotransmitter systems (i.e. mechanistic 26 convergence). However, pharmacological mechanisms for stimulant effects were varied even 27 within families suggesting that stimulant chemicals may be more evolutionarily labile than those 28 associated with hallucinogenic and sedative effects. Our study has shown that phylogenetic 29 analyses of traditionally used psychoactive plants suggests multiple ethnobotanical origins and 30 widespread human dependence on these plants for survival, motivating pharmacological 31 investigation into their potential as modern therapeutics for various neurological disorders. 32 33 Keywords: drug discovery, ethnopharmacology, evolutionary ethnobiology, 34 neuropsychopharmacology, psychotropic, traditional medicine 35 36 Introduction 37 Plants constantly evolve to produce various defensive secondary metabolites against their 38 equally adaptive predators (Polya, 2003; Wink, 2003). Some well-known psychoactive 39 compounds such as atropine, caffeine, cocaine, nicotine and morphine are believed to have been 40 products of this evolutionary arms race (Howe & Jander, 2008; Fürstenberg-Hägg, Zagrobelny, 41 & Bak, 2013). Psychoactive, alternatively psychotropic, substances act on the nervous system 42 affecting mental processes and behavior (Spinella, 2001; Rätsch, 2005). They include 43 hallucinogens that distort reality, sedatives/narcotics that induce sleep, calmative or anxiolytics, 44 antidepressants, stimulants that wake the mind, and even aphrodisiacs that promote sexual 45 arousal. Interestingly, humans have exploited alternate uses for plants containing psychoactive 46 phytochemicals that have purportedly evolved to ward off plant predators. However, the affinity 2 PeerJ reviewing PDF | (2016:06:11617:0:0:CHECK 26 Jun 2016) Manuscript to be reviewed 47 of these phytochemicals within the hominid nervous system may also indicate some kind of 48 mutualistic co-evolution, with ancient humans seeking and perhaps cultivating plant 49 psychotropics to facilitate survival, by alleviating starvation, fatigue and pain (Sullivan & Hagen, 50 2002). 51 Psychoactive compounds have specific molecular targets in the nervous system, and 52 interact in a particular way with neuronal receptors to produce various psychoactive effects 53 (Spinella, 2001; Polya, 2003). For instance, morphine in opium poppy (Papaver somniferum, 54 Papaveraceae) eliminates pain by binding to opioid receptors (Polya, 2003), but simultaneously 55 promotes sedation and euphoria, by disinhibiting dopamine-containing neurons in the limbic 56 system (Johnson & North, 1992). Dopamine is ultimately responsible for feelings of elation and 57 satisfaction, which occur after some rewarding act like sex or food satiety. Addiction arises from 58 wanting to re-experience the pleasure due to the drug’s ability to cause dopamine buildup 59 (Lüscher and Ungless, 2006). Compounds that mimic serotonin and act as receptor agonists like 60 mescaline in the peyote cactus (Lophophora williamsii, Cactaceae), trigger hallucinations and 61 cognitive breakdown (Polya, 2003). Stimulating substances, such as the alkaloid nicotine