OPEN Foundation

New substances

Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties

November 7, 2014 / Chemistry, Ethnobotany, New substances, Other subjects, Other substances, Papers, Publications / By / , , , , ,

Abstract

Dictyonema huaorani, a new species represented by a well-developed specimen found in the Ecuadorian Amazon region, is described in this paper. The material was collected during a Harvard ethnobotanical expedition in 1981 and originally determined by Mason E. Hale Jr. as belonging in the genus Dictyonema (D. sericeum s.lat.) and possibly representing an undescribed species. The species is morphologically distinctive in forming densely woven, semicircular thalli, closely resembling those of the paleotropical D. ligulatum but lacking clamps and with hyphal sheath around the photobiont filaments that resembles those of Cyphellostereum species. The species was reported to have hallucinogenic properties and chemical analyses suggest certain substances present that are shared with the hallucinogenic mushroom Psilocybe cubensis. Due to our inability to use pure reference compounds and scarce amount of sample for compound identification, however, our analyses were not able to determine conclusively the presence of hallucinogenic substances.

Schmull, M., Dal-Forno, M., Lücking, R., Cao, S., Clardy, J., & Lawrey, J. D. (2014). Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties. The Bryologist, 117(4), 386-394. http://dx.doi.org/10.1639/0007-2745-117.4.386

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Michael acceptor approach to the design of new salvinorin A-based high affinity ligands for the kappa-opioid receptor

October 6, 2014 / Chemistry, New substances, Other substances, Papers, Psychopharmacology, Publications, Salvia / Salvinorin A / By / , , , , ,

Abstract

The neoclerodane diterpenoid salvinorin A is a major secondary metabolite isolated from the psychoactive plant Salvia divinorum. Salvinorin A has been shown to have high affinity and selectivity for the κ-opioid receptor (KOR). To study the ligand–receptor interactions that occur between salvinorin A and the KOR, a new series of salvinorin A derivatives bearing potentially reactive Michael acceptor functional groups at C-2 was synthesized and used to probe the salvinorin A binding site. The κ-, δ-, and μ-opioid receptor (KOR, DOR and MOR, respectively) binding affinities and KOR efficacies were measured for the new compounds. Although none showed wash-resistant irreversible binding, most of them showed high affinity for the KOR, and some exhibited dual affinity to KOR and MOR. Molecular modeling techniques based on the recently-determined crystal structure of the KOR combined with results from mutagenesis studies, competitive binding, functional assays and structure–activity relationships, and previous salvinorin A–KOR interaction models were used to identify putative interaction modes of the new compounds with the KOR and MOR.

Polepally, P. R., Setola, V., Vardy, E., Roth, B. L., Mosier, P. D., & Zjawiony, J. (2014). Michael Acceptor Approach to the Design of New Salvinorin A-Based High Affinity Ligands to the Kappa-Opioid Receptor. Planta Medica, 78(5), 818-829. https://dx.doi.org/10.1016/j.ejmech.2014.07.077
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Iboga-Type Alkaloids from Ervatamia officinalis

August 5, 2014 / Chemistry, Ethnobotany, Iboga / Ibogaine, New substances, Other subjects, Other substances, Papers, Publications / By / , , , , , ,

Abstract

Seven new iboga-type alkaloids, ervaoffines A–D (1–4), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1–7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed.

Tang, B. Q., Wang, W. J., Huang, X. J., Li, G. Q., Wang, L., Jiang, R. W., … & Ye, W. C. (2014). Iboga-Type Alkaloids from Ervatamia officinalis. Journal of natural products, 77(8), 1839-1846. https://dx.doi.org/10.1021/np500240b
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From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs

March 26, 2014 / Ketamine, New substances, Other disciplines, Other substances, Papers, Publications / By / ,

Abstract

PCP or phencyclidine was discovered in 1956 and soon became a popular street drug. Dissociatives including PCP, ketamine, and dextromethorphan have been used non-medically for their mind-altering effects for over 60 years. Many of these compounds have also been used clinically and in legitimate research. At least 14 derivatives of PCP were sold for non-medical and illict use from the late 1960s until the 1990s. With the advent of the Internet, the drug market underwent a dramatic evolution. While initially gray-market chemical vendors offering dextromethorphan and ketamine thrived, most recently the market has shifted to legal high and online-based research chemical vendors. Starting with the first dissociative research chemical, 4-MeO-PCP in 2008, the dissociative research chemical market has rapidly evolved and currently comprises at least 12 dissociatives, almost half of which were unknown in the scientific literature prior to their introduction. Several of these, including methoxetamine, have reached widespread use internationally. A historical account of non-medical use of over 30 dissociative compounds was compiled from a diverse collection of sources. The first complete portrait of this underground market is presented along with the relevant legal, technological, and scientific developments which have driven its evolution.

Morris, H., & Wallach, J. (2014). From PCP to MXE: a comprehensive review of the non‐medical use of dissociative drugs. Drug testing and analysis, 6(7-8), 614-632. http://dx.doi.org/10.1002/dta.1620
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Survey: New Drugs for Mental Health

December 6, 2021 / Articles, New substances, Publications, Research / By

After the recent published study on psychedelic substances and mental health, researchers are looking to explore this relation more deeply. The main aim of the survey is to gain novel insight towards un-noted benefits (and harms) of recreationally used drugs on mental health.

This survey was created by Imperial college, Prof D. Nutt, Dr R. Carhart-Harris and their team. According to the researchers, little is yet known about the effects on mental health of people who experiment with psychedelic substances. They are asking questions to gather information about potential usefulness for mental health of these new drugs and also to discover whether they have any unrecognised negative effects. Please click this link to participate in this recently launched online survey regarding psychoactive drugs and mental health.

Participants can fill in a different survey for each drug they want to say something about. Please only complete a survey if you have personal experience with a particular drug.

Responses will be treated as clinical information and are protected by medical confidentiality law. Your personal details will not be requested or stored.

Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a “Legal High” from the Internet

August 2, 2013 / Addiction, New substances, Other disciplines, Other subjects, Other substances, Papers, Personal development, Publications / By / ,

Abstract

Methoxetamine (MXE), a ketamine analogue, is one of the new “legal highs” sold on the Internet. The aim of this qualitative study was to provide an initial understanding of what characterizes the experiences induced by MXE. Anonymously written reports (33 persons) on the effects of MXE were collected from public Internet forums and analyzed using the Empirical Phenomenological Psychological Method. The analysis generated 10 themes: (1) preparation, motivation and anticipation; (2) initial effects; (3) malfunction of cognitive processes stabilizing normal state; (4) inner personal processes and learning; (5) emotional processes; (6) altered sensory perception; (7) dissolution and transition; (8) spiritual and transcendental experiences; (9) effects and processes after the experience; (10) re-dosing and addiction.

MXE induced a heavily altered state of consciousness. The effects were similar to those induced by classic hallucinogens (such as LSD, psilocybin) and the dissociative ketamine. MXE seemed to have quite a high abuse potential. Beside the positive effects described, negative effects like fear and anxiety were also reported. Acceptance was considered the best coping strategy. Dissolution of identity and body often culminated in spiritual and transcendental experiences. More research is needed on safety issues, how to minimize harm, and the motivation for using legal highs.

Kjellgren, A., & Jonsson, K. (2013). Methoxetamine (MXE)–a phenomenological study of experiences induced by a “legal high” from the Internet. Journal of psychoactive drugs, 45(3), 276-286. http://dx.doi.org/10.1080/02791072.2013.803647

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2C or not 2C: phenethylamine designer drug review

June 9, 2013 / New substances, Other disciplines, Other substances, Papers, Psychopharmacology, Publications, Safety, Toxicology / By / , , ,

Abstract

New groups of synthetic “designer drugs” have increased in popularity over the past several years. These products mimic the euphoric effects of other well-known illicit drugs but are advertised as “legal” highs and are sold over the internet, at raves and night clubs, and in head shops. The 2C series drugs are ring-substituted phenethylamines that belong to a group of designer agents similar in structure to 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy). Understanding the pharmacology and toxicology of these agents is essential in order to provide the best medical care for these patients. This review focuses on the pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication based on available published literature. Multiple names under which 2C drugs are sold were identified and tabulated. Common features identified in patients intoxicated with 2Cs included hallucinations, agitation, aggression, violence, dysphoria, hypertension, tachycardia, seizures, and hyperthermia. Patients may exhibit sympathomimetic symptoms or symptoms consistent with serotonin toxicity, but an excited delirium presentation seems to be consistent amongst deaths attributed to 2C drugs; at least five deaths have been reported in the literature in patients intoxicated with 2C drugs. 2C drugs are a group of designer intoxicants, many of which are marketed as legal, but may carry risks that consumers are unaware of. These drugs may be characterized by either serotonergic toxicity or a sympathomimetic toxidrome, but a presentation consistent with excited delirium is consistent amongst the reported 2C-related deaths. Treatment of 2C intoxication is primarily supportive, but immediate action is required in the context of excited delirium, hyperthermia, and seizure activity.

Dean, B. V., Stellpflug, S. J., Burnett, A. M., & Engebretsen, K. M. (2013). 2C or not 2C: phenethylamine designer drug review. Journal of Medical Toxicology, 9(2), 172-178. 10.1007/s13181-013-0295-x
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The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor

March 19, 2013 / Ketamine, Neuroscience, New substances, Other substances, Papers, Psychopharmacology, Publications / By / , , , , , ,

Abstract

In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as ‘designer drugs’ and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)–2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X. P., Setola, V., Treble, R., & Iversen, L. (2013). The ketamine analogue methoxetamine and 3-and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One, 8(3), e59334. http://dx.doi.org/10.1371%2Fjournal.pone.0059334
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Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden

August 29, 2011 / New substances, Other substances, Papers, Phenomenology, Psychology, Publications / By / ,

Abstract

The psychoactive substance 4-HO-MET (4-hydroxy-N-methyl-N-ethyltryptamine) with psychedelic qualities is one of many legal so-called Internet drugs. The aim of this qualitative study was to establish an understanding of what characterizes its recreational use. Very little is known about the effects of this substance. Twenty-five anonymous Swedish experience reports (from persons aged 18–30 years) from public Internet forums were analyzed using the Empirical Phenomenological Psychological Method. The analysis produced 37 categories that were compiled into nine general themes: (1) motivation, preparation and expectation; (2) initial effects; (3) change of perception; (4) unfiltered awareness and intensified flow of information; (5) lateral cognition; (6) border between subject and object is erased; (7) heaven; (8) hell; and (9) subsiding effects. An understanding of the chronological happenings, called The Process, appeared out of the general structure. Drastic changes in cognitive, emotional and bodily functions were described. The motivation for use seemed to be driven by a strong curiosity. The experiences shifted between “heaven” and “hell,” but participants appeared satisfied and ready to repeat the experience. The experiences described show great similarity with classic psychedelic substances as LSD or psilocybin. More research is needed about health hazards or possible therapeutic potentials.

Kjellgren, A., & Soussan, C. (2011). Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden. Journal of Psychoactive Drugs, 43(3), 211-219. http://dx.doi.org/10.1080/02791072.2011.605699
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Comparative potencies of MDMA analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines

December 1, 2007 / Chemistry, MDMA, New substances, Other subjects, Other substances, Papers, Psychopharmacology, Publications / By / , , , , ,

Abstract

Background and purpose:Illegal ‘ecstasy’ tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT).

Experimental approach:Concentration–response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy 3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl- N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA).

Key results: 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT.

Conclusions and implications: This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.

Montgomery, T., Buon, C., Eibauer, S., Guiry, P. J., Keenan, A.K., & McBean, G. J. (2007). Comparative potencies of MDMA analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. British Journal of Pharmacology, 152(7), 1121–1130. http://dx.doi.org/10.1038/sj.bjp.0707473
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30 April - Q&A with Rick Strassman

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