OPEN Foundation

Other substances

The induction of synaesthesia with chemical agents: a systematic review

October 17, 2013 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

Despite the general consensus that synaesthesia emerges at an early developmental stage and is only rarely acquired during adulthood, the transient induction of synaesthesia with chemical agents has been frequently reported in research on different psychoactive substances. Nevertheless, these effects remain poorly understood and have not been systematically incorporated. Here we review the known published studies in which chemical agents were observed to elicit synaesthesia. Across studies there is consistent evidence that serotonin agonists elicit transient experiences of synaesthesia. Despite convergent results across studies, studies investigating the induction of synaesthesia with chemical agents have numerous methodological limitations and little experimental research has been conducted. Cumulatively, these studies implicate the serotonergic system in synaesthesia and have implications for the neurochemical mechanisms underlying this phenomenon but methodological limitations in this research area preclude making firm conclusions regarding whether chemical agents can induce genuine synaesthesia.

Luke, D. P., & Terhune, D. B. (2013). The induction of synaesthesia with chemical agents: a systematic review. Frontiers in Psychology, 4, 1-11. http://dx.doi.org/10.3389/fpsyg.2013.00753
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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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Effects of Schedule I drug laws on neuroscience research and treatment innovation

June 12, 2013 / Ayahuasca, Cacti / Mescaline, DMT, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Other disciplines, Other subjects, Other substances, Papers, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Many psychoactive drugs are used recreationally, particularly by young people. This use and its perceived dangers have led to many different classes of drugs being banned under national laws and international conventions. Indeed, the possession of cannabis, 3,4‑methylenedioxy‑N‑methylamphetamine (MDMA; also known as ecstasy) and psychedelics is stringently regulated. An important and unfortunate outcome of the controls placed on these and other psychoactive drugs is that they make research into their mechanisms of action and potential therapeutic uses — for example, in depression and post‑traumatic stress disorder — difficult and in many cases almost impossible.

Nutt, D. J., King, L. A., & Nichols, D. E. (2013). Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nature Reviews Neuroscience, 14, 577-585. http://dx.doi.org/10.1038/nrn3530
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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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Hallucinogen persisting perception disorder: what do we know after 50 years?

March 1, 2013 / Cacti / Mescaline, DMT, HPPD, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By / ,

Abstract

‘Flashbacks’ following use of hallucinogenic drugs have been reported for decades; they are recognized in DSM-IV as ‘Hallucinogen Persisting Perception Disorder (Flashbacks)’, or HPPD. We located and analyzed 20 quantitative studies between 1955 and 2001 examining this phenomenon. However, many of these studies were performed before operational criteria for HPPD were published in DSM-III-R, so they are difficult to interpret in the light of current diagnostic criteria. Overall, current knowledge of HPPD remains very limited. In particular (1) the term ‘flashbacks’ is defined in so many ways that it is essentially valueless; (2) most studies provide too little information to judge how many cases could meet DSM-IV criteria for HPPD; and consequently (3) information about risk factors for HPPD, possible etiologic mechanisms, and potential treatment modalities must be interpreted with great caution. At present, HPPD appears to be a genuine but uncommon disorder, sometimes persisting for months or years after hallucinogen use and causing substantial morbidity. It is reported most commonly after illicit LSD use, but less commonly with LSD administered in research or treatment settings, or with use of other types of hallucinogens. There are case reports, but no randomized controlled trials, of successful treatment with neuroleptics, anticonvulsants, benzodiazepines, and clonidine. Although it may be difficult to collect large samples of HPPD cases, further studies are critically needed to augment the meager data presently available regarding the prevalence, etiology, and treatment of HPPD.

Halpern, J. H., & Harrison, G. P. Jr. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and Alcohol Dependence, 69(2), 109-119. http://dx.doi.org/10.1016/S0376-8716(02)00306-X
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Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

January 29, 2013 / Cacti / Mescaline, Neuroscience, Other subjects, Other substances, Papers, Psychopharmacology, Publications / By / , ,

Abstract

The 5-HT2A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT2A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT2A/2C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT2A knockout mice, indicating the effect is a consequence of 5-HT2A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT2A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1–10 mg/kg i.p.). The selective 5-HT2A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT2A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT2A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT2A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT2A activation and hallucinogenesis.

Halberstadt, A. L., Powell, S. B., & Geyer, M. A. (2013). Role of the 5-HT 2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice. Neuropharmacology, 70, 218-227. 10.1016/j.neuropharm.2013.01.014
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Quantitative Analysis of Narrative Reports of Psychedelic Drugs

June 1, 2012 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Other disciplines, Other subjects, Other substances, Papers, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Background

Psychedelic drugs facilitate profound changes in consciousness and have potential to provide insights into the nature of human mental processes and their relation to brain physiology. Yet published scientific literature reflects a very limited understanding of the effects of these drugs, especially for newer synthetic compounds. The number of clinical trials and range of drugs formally studied is dwarfed by the number of written descriptions of the many drugs taken by people. Analysis of these descriptions using machine-learning techniques can provide a framework for learning about these drug use experiences.

Methods

We collected 1000 reports of 10 drugs from the drug information website Erowid.org and formed a term-document frequency matrix. Using variable selection and a random-forest classifier, we identified a subset of words that differentiated between drugs.

Results

A random forest using a subset of 110 predictor variables classified with accuracy comparable to a random forest using the full set of 3934 predictors. Our estimated accuracy was 51.1%, which compares favorably to the 10% expected from chance. Reports of MDMA had the highest accuracy at 86.9%; those describing DPT had the lowest at 20.1%. Hierarchical clustering suggested similarities between certain drugs, such as DMT and Salvia divinorum.

Conclusion

Machine-learning techniques can reveal consistencies in descriptions of drug use experiences that vary by drug class. This may be useful for developing hypotheses about the pharmacology and toxicity of new and poorly characterized drugs.

Coyle, J. R., Presti, D. E., Baggott, M. J. (2012). Quantitative Analysis of Narrative Reports of Psychedelic Drugs.
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Genuine and drug-induced synesthesia: a comparison

April 21, 2012 / Other substances, Papers, Phenomenology, Psychology, Publications / By / , , , , ,

Abstract

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia (genuine, acquired and drug-induced). This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed.

Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity.

Sinke, C., Halpern, J. H., Zedler, M., Neufeld, J., Emrich, H. M., & Passie, T. (2012). Genuine and drug-induced synesthesia: a comparison. Consciousness and cognition, 21(3), 1419-1434. http://dx.doi.org/10.1016/j.concog.2012.03.009
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A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010

February 28, 2012 / Chemistry, DMT, Other subjects, Other substances, Papers, Publications / By / , ,

Abstract

Three indole alkaloids that possess differing degrees of psychotropic/psychedelic activity have been reported as endogenous substances in humans; N,N-dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT), and 5-methoxy-DMT (MDMT). We have undertaken a critical review of 69 published studies reporting the detection or detection and quantitation of these compounds in human body fluids. In reviewing this literature, we address the methods applied and the criteria used in the determination of the presence of DMT, MDMT, and HDMT. The review provides a historical perspective of the research conducted from 1955 to 2010, summarizing the findings for the individual compounds in blood, urine, and/or cerebrospinal fluid. A critique of the data is offered that addresses the strengths and weaknesses of the methods and approaches to date. The review also discusses the shortcomings of the existing data in light of more recent findings and how these may be overcome. Suggestions for the future directions of endogenous psychedelics research are offered.

Barker, S. A., McIlhenny, E. H., Strassman, R. (2013). A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. Drug Testing and Analysis, 4(7-8), 617-35. http://dx.doi.org/10.1002/dta.422
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