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Review Article Mini Review on Psychedelic : Illumination on the Hidden Aspects of Mind

Lemlem Hussien Salih and Atul Kaushik*

Department of Medicinal , School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea

ABSTRACT

Psychedelics constitute a class of psychoactive drugs with unique effects on . Psychedelic means mind/soul "revealing" and refers to the ability of these drugs to illuminate normally hidden aspects of mind or psyche. Many psychedelic agents occur in nature; others are synthetically produced. Naturally occurring psychedelic drugs have been inhaled, ingested, worshiped, and reviled since Address for prehistory. The phenomenology of the hallucinogenic is Correspondence extremely complex, sensory, emotional, cognitive, and spiritual, levels. Most psychedelic drugs structurally resemble with Department of : , two (nor , epinephrine and ), and . These structural School of Pharmacy, similarities lead to three classes for categorizing psychedelic drugs: Asmara College of , -like, and serotonin-like. And also a Health Sciences, fourth class of psychedelic drugs can be included, the psychedelic Asmara, Eritrea anesthetics. This mini review focuses on pharmacological and Tel.- +291-1-186041 medicinal aspects of this class. E-mail: atul_kaushik29 Keywords: Psychedelic drugs, Pharmacological features of @rediffmail.com psychedelic drugs, SAR of psychedelic drugs.

INTRODUCTION "Rational consciousness...is but one produced. Naturally occurring psychedelic special type of consciousness, whilst all drugs have been inhaled, ingested, about it, parted from it by the filmiest of worshiped, and reviled since prehistory. screens; there lie potential forms of Native American shamans consumed consciousness entirely different."-William psychedelic such as the James. Psychedelics constitute a class of (contains ), "magic" psychoactive drugs with unique effects on (contains ), or the consciousness. Psychedelic means mind/soul brew called (contains DMT and "revealing" and refers to the ability of these ) in order to communicate with drugs to illuminate normally hidden aspects God or the spirit realm. By supplying that of mind or psyche. Many psychedelic agents stimulus, psychedelic drugs provide an occur in nature; others are synthetically instrument for experimental investigation of

American Journal of Phytomedicine and Clinical Therapeutics www.ajpct.org Kaushik et al______ISSN 2321 – 2748 what have come to be called altered states of The is consciousness (ASC). And shall examine relatively new to industrial cultures, and has what they have to teach us about historically been at odds with centralized , , , birth and forms of government. Except for the death, artistic and scientific creation, and the accidental discovery of LSD in 1943, roots of religious belief (Photograph). knowledge of psychedelic agents have come as legacies of ancient American religions, Historical Background where these psychic effects are considered These drugs can induce to be of a divine or holy in nature3-6. , separating people who use Just over 110 years ago, the German them from reality. Because of the wide pharmacologist Arthur Heffter began a range of psychological effect they produce, systematic investigation into the isolated the single term that might best be used to components of 'peyote' ( classify these agents has long been debated. williamsii) by ingesting a series of these The term is used because these himself. Subsequently, mescaline agents can, in high enough doses, induce was identified as the active component of hallucinations. However, the term is this North American cactus, which had been somewhat inappropriate because illusory used since pre-Columbian as a phenomena and perceptual distortions are psychoactive sacrament. Peyote persists as more common than are true hallucinations. the central sacrament of several native The term has also been religions in and the U.S. used because of the alleged ability of these Following the discovery of LSD, drugs to mimic psychoses or induce and its ester (psilocybin) psychotic states. However, most of these were both isolated from the fungi Psilocybe drugs do not produce the same behavioral mexicana and synthesized in the late 1950s7. patterns that are observed in people who Again, the active components were only experience psychotic episodes. Others have identified by experimentation, after used a descriptive term, such as animal testing gave ambiguous results. To phantasticum or psychedelic to imply that complete the study, synthetic psilocybin was these agents all have the ability to alter returned to the village of Huatla de Jimenez sensory . In this article the term in Oaxaca, Mexico, its place of botanical psychedelic is used because it allows for origin, and given to the shaman more flexibility in grouping together a María Sabina who confirmed the synthetic disparate array of effects into a quantifiable substance to be "the same God" she had and recognizable syndrome1. Abraham, previously known only through the Aldridge, and Gogia2 define a psychedelic mushroom8. as “any agent that causes alterations in Throughout the 1950s psychedelics , cognition, and as its became an obvious and powerful influence primary psychobiological actions in the on the growing field of molecular presence of an otherwise clear sensorium.” , initially as models for This definition separates the pure and eventually as adjuncts to . psychedelic drugs from other substances that At the same , chemical warfare can cause altered states of thinking and researchers explored these compounds for perception, such as that the their potential as "truth serums" and adjuncts mind and that produce clouding of to "brain washing"6,9. Through both military consciousness and amnesia. and medical channels, these substances then

AJPCT[1][5][2013]432-444 Kaushik et al______ISSN 2321 – 2748 began to surface in artistic and intellectual normal alterations in sensory, emotional and circles throughout the world. And in spite of cognitive effects. The most positive proscription of some psychedelic drugs, accounts describes mystical revelations such popular experimentations have still as gaining direct knowledge of God or an continued. all- encompassing cosmic unity. More commonly reported is a kaleidoscopic CHARACTERISTIC FEATURES display of intensely colorful visions, ranging from continuously unfolding abstract The phenomenology of the designs to fully formed images of animals, hallucinogenic experience is extremely plants, landscapes or more bizarre scenes. complex, operating, again, at physiological, They also enhance ; enhance the sensory, emotional, cognitive, and we could operation of the mind and , and say, spiritual, levels. Psychedelics induced produce effects highly therapeutic for the alterations are so drastic from our normal psychological growth of the individual10. states of consciousness, that, again, we may Psychedelic drugs are not addictive. call the state induced by an Even enthusiastic proponents of Altered State Conciousness (ASC). psychedelics take them infrequently due to The physiological effects of the intensity of the “trip.” Animal research hallucinogenic induced ASC are reasonably indicates that Homo sapiens are the only straight-forward: dilate, rate species that will voluntarily take a increases, breathing patterns are altered, again after having chills and are experienced, experienced the effects. Although laboratory spontaneous motor motions such as dance animals such as rats or monkeys will readily and gestures may result, and sleeping is self-administer most other drugs abused by significantly impaired. The controversy , including , , begins when we go beyond the obvious , and , they physiological symptoms of these drugs. At find psychedelic drugs highly aversive sensory, emotional and cognitive levels a (Yokel, 1987). wide variety of conflicting reports exist. Perhaps the easiest way to conceptualize the PHARMACOLOGICAL FEATURES variety of views of the effects of psychedelic drugs is to realize that they lie along a Mounting evidence continues to spectrum. show strong correlations between At one extreme of this spectrum, the activity and behavior; however, the psychic effects of psychedelics are viewed in a effects are not contained within the negative light and thought of as a chemistry of these or any other, neuropathology; sensory alterations; psychoactive drugs. Instead, 'hallucinations', emotional changes are seen interactions are thought to affect neuronal to be related to and the disjointed activity, and receptor sites for neuroactive behavior of schizophrenics, and cognitive compounds are one substrata of the neural alterations are considered to be . circuitry which leads to mental activity. As Thus, to some, all alterations caused by with other drugs, the psychedelics may psychedelics are considered subnormal or become ionized in receptor sites to form pathological. charge transfer complexes, thus modifying At the opposite extreme of the the local flow of electrons and, spectrum, psychedelic effects are viewed in subsequently, the transmission of neuronal a positive light and associated with super- information31, 32.

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Typical Pharmacologic Effects PCP), which exert their psychedelic actions Associated with Psychedelic Activity: by affecting a specific subclass of glutamate  Pupillary dilation at full /effect receptors, the NMDA receptors.  Cross tolerance between other members However, with few exceptions, the (rare exceptions) chemistry of psychedelic compounds can be  Tolerance not overcome by increasing categorized as either indolealkylamines (i.e., dosage (rare exceptions) as or ) or 11  Not “addictive”, i.e., no withdrawal . Stereochemical aspects are also important for psychoactivity, and effects after discontinuing use 12,13  Not associated with compulsive use have already been mentioned below .  Strong activity, both “agonistic” and “antagonistic” A. -alkyl-  Often a loss of during the Indole alkaloids are found in many plants, animals, and several microorganisms. experience They account for about one quarter of the  Heightened ; sleep is often known alkaloids. Many that have impossible known neuroactive properties carry an  Toxic doses are essentially unknown, 38 aliphatic at position 3 on the except with some phenethylamines . indole ring (Figure 1). A large portion of Chemical similarities and psychedelic agents are tryptamines, where interactions with other neurotransmitters the ethylamine side-chain is alkylated and may account for variations in effect between has a relatively wide range of molecular indolealkylamines, , and motion. Important substitution sites that phenethylamines. In very general terms, the determine psycho activity are on the indole psychedelics are said to be ring, the side-chain carbons, and the more energetic, sensual, empathogenic, or aliphatic . N, N-Di- entactogenic, while psychedelics methyltryptamines (DMTs) provide the most are thought to be more hallucinogenic, remarkable effects in this series (Figure.1), disorienting, and somatically heavy. These where only psilocin and psilocybin show descriptions are very broad, but this is the oral activity. 5-HT receptor subtype popular distinction made between the two differentiation among several N, N- major classes of psychedelics. dialkylated tryptamines has been reported14. A listing of psychedelic indolealkylamines, CHEMISTRY AND typical human dosages, and notable receptor ACTIVITY RELATIONSHIPS binding sites are presented in Table 1. N-Alkyl homologues of DMT, in Most psychedelic drugs structurally which the N, N-dimethyl are resemble one of four neurotransmitters: replaced with longer and more hydrophobic acetylcholine, two catecholamines aliphatic moieties, include the diethyl-, ( and dopamine), and dipropyl-, diisopropyl and diallyltryptamines. serotonin. These structural similarities lead All of these derivatives are psychoactive in to three classes for categorizing psychedelic humans, and most are orally active. drugs: anticholinergic, catecholamine-like, Qualitatively, homologation of the N, N- and serotonin-like. And also a fourth class of dialkyl substituents attenuates the intensity of psychedelic drugs can be included, the the experience, and prolongs the course of psychedelic anesthetics (eg. - action. Nonsymmetrical alkyl substitution of

AJPCT[1][5][2013]432-444 Kaushik et al______ISSN 2321 – 2748 the side-chain nitrogen (e.g., methyl also present in at least 95 other species of isopropyl- or methyl ethyl-) also yields orally which are found throughout the active compounds with threshold doses and world. Both are orally active and epitomize qualitative actions similar to those of their N, the psychedelic effect for tryptamines. As a N-dimethyl derivatives15. , psilocybin is quickly converted by In general, at the 4- the body to psilocin. Neither compound has position on the indole ring, as in the known . As a natural product, often prototypical compound psilocin, enhances the known as "magic" mushrooms, these two of N, N-dialkyl homologues and non alkaloids may be the most widely used and symmetric N-alkylated derivatives by readily available psychedelic agents. The approximately an order of magnitude, subjective effects are relatively short compared to the unsubstituted derivatives. compared to LSD or mescaline, though fairly Methoxylation at the 5-position on the indole long when compared with other ring similarly increases potency but also dimethyltryptamines. Both have high affinity enhances the stimulatory ("amphetamine- for 5-HT1A and 5-HT2 sites (Figure1)14. like") effects while attenuating visual effects. Derivatives with 6-, 7-methoxy-, 5, 6- 2. Di-Methyl Trytamine dimethoxy-, 5,6-methylenedioxy substituents N, N-Dimethyltryptamine (DMT) is also display greatly attenuated activity. agonistic at 5-HT1A and 5-HT1C and Methyl substitution on tryptamine's antagonistic at 5-HT2 sites, though may also show partial 5-HT2 agonistic activity (Figure side-chain, at the α-carbon, also results in 14, 17 orally active psychotropic compounds. 1, Table. 1) . It is not orally active, due to Racemic N1-n-propyl-5-methoxy-α- its rapid oxidation by type A monoamine methyltryptamine, for example, has been oxidase (MAO-A). It was first identified as a reported to bind with high affinity and component of cohoba, a psychotropic snuff significant selectivity to 5-HT2 receptors16. α- prepared from the of Methyl tryptamine, itself, and its 5-methoxy- peregrina (formerly peregrina) in and 4-hydroxy- congeners are orally active in 1955. Although it had been synthesized 24 years earlier, its psychoactivity was not humans at the 3 to 30mg level. α-substituted 18 tryptamines are the only enantiomeric reported until 1956 . DMT occurs in trace derivatives in this class that have been amounts in mammals, including humans, empirically investigated and, in general, the where it putatively functions as a trace /neuromodulator, and can be S-(+) enantiomers are more potent than the R- 19 (-) enantiomers in human and other animal injected, smoked, or insufflated . It is experiments. α-Methytryptamine and α- originally derived from the essential amino ethyltryptamine are competitive inhibitors of and ultimately produced by the INMT during normal (MAO), and this 39 property may account for their oral activity, . The most outstanding effect as well as their prolonged duration of action from this simple tryptamine is the explosion relative to other psychoactive tryptamines. of visual imagery, primarily scintillating colored patterns, for only a few minutes after 1. Psilocin and Psilocybin administration. This effect is almost absent in These two di-methyltryptamines were emotive content, perhaps due to the brevity first isolated from the mushroom Psilocybe and intensity of visual phenomenon. Mexicana7 and named in 1958 by Swiss chemist . These alkaloids are

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3. MEO-DMT been used since antiquity as an abortifacient. 5-Methoxy-DMT (5-MeO-DMT) was Ergotamines are now known to be powerful first synthesized in 1936, and in 1959 it was contractors of the uterus, a tissue rich in 5-HT isolated as one of the psychoactive receptors. The tetracyclic ring system ingredients of is represented by LSD (Figure 1), and related seeds used in preparing Yopo snuff. It is a full derivatives are known more specifically as at 5-HT1A, 5-HT1C, 5-HT1D, and 5- lysergamides. HT2 sites (Figure 1, Table. 1)14,20. Like DMT, Although first synthesized in 1938 as it is also found as a component of traditional the 25th derivative in a series of psychoactive snuffs from the Americas, and lysergamides, LSD ( the psychoactive effects are short. It is active Diethylamide), was not until 1943 that Albert orally, when taken with a MAOI, but Hofmann inadvertently absorbed enough d- according to numerous reports, the LSD-25 to notice its psychoactive potential22. combination with MAOI is extremely Subsequent investigations confirmed this unpleasant and has a strong . activity. At the time it was the most potent Additional mechanisms of action such as neuroactive substance known, being active at inhibition of MAOI may be involved also. less than 1μg/kg. LSD is a full 5-HT1A According to the researcher , 5- agonist, partial/weak 5-HT2 MeO-DMT is active orally with doses over agonist/antagonist17, with additional affinity 30 mg without aid of an MAOI. Unlike DMT, at 5-HT1D23, and also binds with high affinity however, its primary effect is almost entirely to dopamine (DA) D1 and D2 receptor sites24. devoid of visual content, while an emotive phenomenon predominates. It has been B. PHENETHYLAMINES described as a "near death" experience, though this is certainly psychological as no 1. Mescaline toxicological effects have been demonstrated. Mescaline (3, 4, 5-trimethoxy- Besides being found in plants, 5-MeO-DMT phenylethylamine) is an anomaly among is also produced in the skin of some toads, psychedelic drugs in that the effective dosage particularly Bufo alverius from the deserts of is extremely high, perhaps due to interactions the American Southwest21. Contrary to with MAO (Table. 2). It occurs naturally in popular belief, these toads are not licked, but the peyote cactus (Lophophora williamsii), "milked" for their from the parietal the San Pedro cactus () glands. The collected venom is dried and and in the Peruvian torch (Echinopsis subsequently smoked for psychoactive peruviana), and as well in a number of other effects. members of the Cactaceae family. Even more potent phenethylamines seem to lack 4. LSD (Lysergic Acid Diethylamide) the unique "sparkle" of mescaline, in terms of LSD is a semisynthetic psychedelic psychoactivity; most are drug of the ergoline family, well known for its sympathomimetically more stimulating with psychological effects which can include some component of the full "mescaline" altered thinking processes, closed and open effect25. It is surprising how little receptor eye visuals, , an altered sense of binding data is available for mescaline. time and spiritual , as well as for Modifications to substituents on its key role in 1960s . position 4 of the phenyl ring seem most (), a parasitic that tolerated in terms of maintaining potency with grows on and a few other grasses, has some psychoactivity. Modifications, and

AJPCT[1][5][2013]432-444 Kaushik et al______ISSN 2321 – 2748 especially lengthening, of substituents at in 1974. In Shulgin's book position 2 are most disruptive, and position 5 PiHKAL, the dosage range is listed as 16– is less sensitive to change than position 2 24 mg. It has a similar substitution pattern to (Figure. 2, Table. 2). While the following DOB, though lacks a chiral center on the compounds are not nearly a complete list of ethylamine side chain (Figure 2). This psychotropic phenethylamines, they are simplification is a distinct advantage over representative to some extent. Overall, DOB as it eliminates the possibility of at the α-carbon on the ethlyamine labeling a receptor with a racemic product. chain increases sympathomimetic potency at Both -B and 2C-I have shorter durations of the expense of psychedelic activity, and the action and less sympathomimetic activity than R-(-) enantiomers are generally the more either DOB or DOI25. The subjective effects potent stereoisomers26. Also, 2, 4, 5- of 2C-B have been described as being more substituted compounds are more potent than “tryptamine-like” than other their analogous 3, 4, 5-derivatives27. phenethylamines. Increased lipophilicity of substituents at position 4 may facilitate passive diffusion into 4. MDMA the CNS to interact with a hydrophobic region 3,4-Methylenedioxy-ethamphetamine on the 5-HT receptor28. Substitution at this (MDMA) or commonly referred as Ecstasy, position probably confers metabolic stability was first mentioned in a German patent by blocking oxidation and hydroxylation27. In assigned to E. Merck in 1914. In a review of general, these compounds show agonistic declassified material from military studies, it actions at serotonergic sites. is mentioned as having toxicological effects at high dosages29. This was apparently the first 2. DOB publication of structure-activity relationships 1-(2, 5-Dimethoxy-4-bromophenyl)- among psychoactive phenethylamines. While 2-aminopropane (DOB) has essentially the most psychoactive phenethylamines offer the same psychoactive profile as DOI25. Both are R (-) stereoisomer as the most active form phenyl isopropyl amines having a 2, 4, 5- (e.g., MDA; DOB; DOM Figure. 2 ) , the S substitution pattern, and both are very potent (+) enantiomer is the more potent form of in humans at low dosages (Table. 2, Figure MDMA. The R (-) isomer of MDMA has 2.). Also, the R-(-) enantiomer of each been shown to be the more potent enantiomer compound binds with high affinity and in releasing 5-HT, thus linking psychoactivity selectivity to 5-HT2 receptor subtypes23. for this compound with serotonergic While some psychoactivity from this and function30. related 2, 4, 5-substituted phenylalkylamines may be called “psychedelic”, the most CONCLUSION prominent effect is sympathomimetic stimulation in conjunction with mescaline- Vigorous research into psychedelic like psychoactivity25. At higher dosages, this drugs, which began more than a half-century stimulation tends to dominate more subtle ago, effectively came to a halt in 1970 when overtones of psychoactivity that are certainly Richard Nixon signed the Controlled present and reflective of psychedelic activity. Substances Act, outlawing the most common hallucinogens. But improvements in brain 3. 2C-B imaging, combined with a better 2-(2, 5-Dimethoxy-4-bromophenyl) understanding of , are helping aminoethane (2C-B) was first synthesized by psychedelics regain their status as promising therapeutic agents for curbing ,

AJPCT[1][5][2013]432-444 Kaushik et al______ISSN 2321 – 2748 , , OCD, and other ills. That each works in specific sites and regions "These were considered drugs of abuse, and of the brain, like specific key notes in a piano, were not attractive for researchers," said that further gives rise to desired rhythm of David Nichols, a professor of mental functioning. at Purdue University who synthesized However, since the psychic effects of psilocybin, MDMA, and other psychedelics psychedelic drugs are almost entirely of the for researchers when the drugs were difficult mind, meaningful information on the to obtain and co-founded the Heffter Institute, qualitative effects have not been readily which supports psychedelic research. "Now I obtained from animal studies, as with other would say that in 10 years there might be a drugs; i.e., the existence of “mindfulness” has host of treatments that employ psilocybin or not been sufficiently demonstrated in other related substances for anxiety, depression, and animals and, more to the point, a common addiction." language does not exist between humans and However, though in the future a any other animal to convey such information. breakthrough of psychedelic drugs in the In the absence of a useful experimental treatment of affective disorders and other model, and considering the characteristic lack psychiatric diseases might occur, it won’t be a of with most psychedelic agents, sole solution of complete treatment from further studies into the application of these these disorders. Till date, one of the reasons to drugs should proceed with experiments using the inability to come up to a novel drug that healthy human volunteers. could restore or relatively stabilize the normal functioning of the psychological mind is due REFERENCES to the highly integrated nature of the central and our incomplete 1. T. A. Bowdie et al., “Psychedelic Effects of understanding of its functioning. And as in Healthy Volunteers: various specific molecules (chemical Relationship to Steady-state Plasma messengers, neurotransmitters, …etc) Concentrations,” Anesthesiology 88 (1998): bind to various sites, as molecular 82-88. 2. H. D. Abraham, A. M. Aldridge, and P. “transistors” to modify the flow of neuronal Gogia, “The of information, to work in an orchestral hallucinogens,” harmonious fashion for the proper functioning 14 (1996): 285-298. of the mental health, a specific 3. Ott, J., The Age of & The antagonist/agonist for a certain mediator or Angel’s Dictionary, Natural Product Co., neurotransmitter alone can’t mimic the Kennewick, WA, 1995. normal functioning of the nervous system. 4. Schultes, R. E. and Hofmann, A., The Just as fingers match specific keys on a piano Botany and Chemistry of Hallucinogens, 2nd to transmit music, psychedelic agents bind to Edition, C.C. Thomas, Springfield, IL, 1980. discrete receptor sites and reveal psychic 5. Schultes, R. E., Hofmann, A., Plants of the effects and also, other molecules give rise to Gods. Healing Arts Press, Rochester, VT, 1992. specific behavioral pattern. That’s why a new 6. Ott, J., Pharmacotheon: Entheogenic drugs, approach to treatment strategy of their plant sources and history, Natural psychological disorders could possibly be Product Co., Kennewick, WA, 1993. seen as the combination of different centrally 7. Hofmann, A., Heim, R., Brack, A., Kobel, acting psychotropic drugs and others like H., Frey, A., Oh, H., Petrzilka, T., and Tricyclic , Psychedelic drugs, Troxler, F., Psilocybin und psilocin, zwei Neurokinins, IL-10 (Interleukin-10)…etc. psychotrope Wirkstoffe aus mexikanischen

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29. Hardman, H. F., Haavik, C. O., and Seevers, human cortex, Psychopharmacol, 97, 118, M. H., Relationship of the structure of 1989. mescaline and seven analogs to toxicity and 34. Brawley and Duffield 1972; von Hungen et behavior in five species of laboratory al. 1974; Logan 1975; Bennett and Snyder animals, Tox Appl Pharmacol, 25(2), 299, 1976. 1973. 35. G. J. Marek and G. K. Aghajanian, 30. Nichols, D. E., Lloyd, D. H., Hoffman, A. J., “Indoleamine and the Phenethylamine Nichols, M. B., and Yim, G. K. W., Effects Hallucinogens: Mechanisms of of certain hallucinogenic Psychotomimetic Action, “Drug and Alcohol analogues on the release of [3H]serotonin dependence 51 (1998): 189-198. from rat synaptosomes, J Med Chem, 25, 36. Robert M. Julien, “A Primer of Drug Action- 530, 1982. A concise, nontechnical guide to the actions, 31. Domelsmith, L. N., Eaton, T. A., Houk, K. uses, and side effects of psychoactive drugs.” N., Anderson, G. M., III, Glennon, R. A., 9th edition: 330-363 Gordon Claridge, Shulgin, A. T., Castagnoli, N., Jr., and “Drugs and Human Behavior”; p.101-122. Kollman, P. A., Photoelectron spectra of 37. William A. McKim, “Drugs and Behavior- psychotropic drugs. 6. Relationships between An introduction to behavioral physical properties and pharmacological pharmacology” 5th edition: p.305-329. actions of amphetamine analogues, J Med 38. Steven B. Karch, MD, “Drug Abuse Chem, 24, 1414, 1981. Handbook- Neurochemistry of psychedelic 32. Clare, B. W., Structure-activity correlations drugs” p.498-511. for psychotomimetics: 1. Phenylalkylamines: 39. Barker S.A., Monti J.A., Christian S.T. Electronic, volume, and hydrophobicity (1981). "N, N-dimethyltryptamine: an parameters, J Med Chem 33, 687, 1990. endogenous hallucinogen". International 33. Pierce, P. A. and Peroutka, S. J., Review of Neurobiology. International Hallucinogenic drug interactions with Review of Neurobiology 22: 83–110. neurotransmitter receptor binding sites in doi:10.1016/S0074-7742(08)60291-3. ISBN 978-0-12-366822-6. PMID 6792104.

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Table 1. A Listing of Psychedelic Indolealkylamines, Dosage, Route of Administration, Duration of Action and Notable Receptor Binding Sites

Compound Dose (μg/kg) Route Duration of action Receptor sites LSD 1.5 p.o. 8-12h 5-HT1A, C & D, 5-HT2, DA1 & 2 Psilocin 300 p.o. 3-6h 5-HT1A, 5-HT2 DMT 400 s/i.v. 10-15m 5-HT1A & C, 5-HT2 5-MeO-DMT 200 s/i.v. 10-20m 5-HT1A, C & D, 5-HT2 5-HO-DMT 50 s 10-20m 5-HT1A, C & D, 5-HT2

Abbreviations: oral (p.o.), smoked/insufflated (s), injected (i.v.), hours (h), minutes (m), 5-HT =serotonin, DA = dopamine.

Table 2. A Listing of Phenethylamines (PEA) and Phenylisopropylamines (PIA), Their Substitution Patterns on the Aromatic Ring, Oral Dosage, Duration of Action in Hours and Notable Receptor Binding Sites

Compound Molecular class and Dosage (μg/kg) Duration of action Receptor substitution sites Mescaline PEA 3,4,5 5,000 8-12 5-HT sites MDMA PIA 3,4 1,800 8-12 5-HT1A, 5-HT uptake site 2C-B PEA 2,4,5 300 4-8 5-HT2A and 5-HT2C 2C-I PEA 2,4,5 300 4-8 5-HT2A and 5-HT2C DOB PIA 2,4,5 30 18-30 5-HT2A and 5-HT2C DOI PIA 2,4,5 30 18-30 5-HT2A and 5-HT2C

Illumination of mind aspects.

AJPCT[1][5][2013]432-444 Kaushik et al______ISSN 2321 – 2748

CH2CH2N(CH3)2 HO CH CH NH 2 2 2

N N H H Serotonin (5-HT) DMT (di methyl tryptamine)

OH

CH2CH2N(CH3)2 HO CH2CH2N(CH3)2

N N H H OH Psilocin HO P O O CH2CH3 O CH2CH2N(CH3)2 C N CH2CH3

N N CH H 3 Psilocybin

LSD

H3CO CH2CH2N(CH3)2 N H

N H

5- MeO -DMT

Figure. 1. Structural formulas of serotonin (neurotransmitter) and six serotonin like psychedelic drugs. These six drugs structurally related to the serotonin and are thought to exert their psychedelic actions through alterations of synapses in the brain. Although LSD is structurally much more complex than serotonin, the basic similarity of the two molecules is apparent.

AJPCT[1][5][2013]432-444 Kaushik et al______ISSN 2321 – 2748

NH H C NH 2 2 2 H H3C C NH2 CH2 HO CH

CH2 CH2

H3CO R' = -Br = -I OH OCH3 OH R Norepinephrine Amphetamine 2C-R'

NH2 NH2 NH2

CH2 HC CH3 HC CH3

CH2 CH2 CH2

H CO O 3

R= -CH3 = -Br = -I H3CO OCH3 OCH3 O OCH 3 R Mescaline DOR MDMA

Figure.2. of norepinephrine, amphetamine and four catecholamine like psychedelic drugs. These four drugs are structurally related to norepinephrine and are thought to exert their psychedelic actions by altering the transmission of nerve impulses at norepinephrine and serotonin synapses in the brain.

AJPCT[1][5][2013]432-444