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DMT

Human hallucinogen research: guidelines for safety

July 1, 2008 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Medicine, Mushrooms / Psilocybin, Neuroscience, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Safety, Salvia / Salvinorin A / By / , ,

Abstract

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (‘bad trip’), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science.

Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety.  Journal of Psychopharmacology, 22(6), 603–620. http://dx.doi.org/10.1177/0269881108093587
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Selective 5-HT2A agonist hallucinogens: A review of pharmacological interaction and corollary perceptual effects

May 23, 2008 / DMT, LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By /

Abstract

The most potent tryptamine hallucinogens – such as DMT, psilocybin, and LSD – are all active at the 5-HT2A receptor subtype and all produce similar visual perceptual results that are immediately recognizable as uniquely psychedelic. Although it is widely accepted that selective serotonin receptor subtype 2A agonism is directly responsible for producing the distinct hallucinations seen on a psychedelic trip, no single theory has yet explained why this is so. Utilizing what we know about psychedelic tryptamine receptor interaction, sensory processing circuits in the neocortex, and EEG scans of psychedelics in action, this review will propose a novel multi-state theory of psychedelic action which invokes a variety of neural processing mechanisms, including phase-coupled neural oscillators; network excitation, disinhibition, and destabilization; recurrent feedback excitation; and neural circuit spike synchrony and brainwave cohesion to close the knowledge gap between the pharmaceutical interactions of selective 5-HT2A hallucinogens, their direct effects on perception and consciousness at varying dose ranges, and their potential long-term adverse effects.

Kent, J. (2008). Selective 5-HT2A agonist hallucinogens: A review of pharmacological interaction and corollary perceptual effects. Beta Review.

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The behavioral pharmacology of hallucinogens

January 1, 2008 / Cacti / Mescaline, Chemistry, DMT, LSD, MDMA, Mushrooms / Psilocybin, Other subjects, Papers, Psychopharmacology, Publications / By / , ,

Abstract

Until very recently, comparatively few scientists were studying hallucinogenic drugs. Nevertheless, selective antagonists are available for relevant serotonergic receptors, the majority of which have now been cloned, allowing for reasonably thorough pharmacological investigation. Animal models sensitive to the behavioral effects of the hallucinogens have been established and exploited. Sophisticated genetic techniques have enabled the development of mutant mice, which have proven useful in the study of hallucinogens. The capacity to study post-receptor signaling events has lead to the proposal of a plausible mechanism of action for these compounds. The tools currently available to study the hallucinogens are thus more plentiful and scientifically advanced than were those accessible to earlier researchers studying the opioids, benzodiazepines, cholinergics, or other centrally active compounds. The behavioral pharmacology of phenethylamine, tryptamine, and ergoline hallucinogens are described in this review, paying particular attention to important structure activity relationships which have emerged, receptors involved in their various actions, effects on conditioned and unconditioned behaviors, and in some cases, human psychopharmacology. As clinical interest in the therapeutic potential of these compounds is once again beginning to emerge, it is important to recognize the wealth of data derived from controlled preclinical studies on these compounds.

Fantegrossi, W. E.,  Murnane, K. S., & Reissig, C. J. (2008). The behavioral pharmacology of hallucinogens. Biochemical Pharmacology 75(1), 17–33. http://dx.doi.org/10.1016/j.bcp.2007.07.018
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Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers

October 1, 2005 / DMT, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , , , , , ,

Abstract

INTRODUCTION:
Pharmacological challenges with hallucinogens are used as models for psychosis in experimental research. The state induced by glutamate antagonists such as phencyclidine (PCP) is often considered as a more appropriate model of psychosis than the state induced by serotonergic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin and N,N-dimethyltryptamine (DMT). However, so far, the psychological profiles of the two types of hallucinogenic drugs have never been studied directly in an experimental within-subject design.

METHODS:
Fifteen healthy volunteers were included in a double-blind, cross-over study with two doses of the serotonin 5-HT2A agonist DMT and the glutamate N-methyl-D-aspartate (NMDA) antagonist (S)-ketamine.

RESULTS:
Data are reported for nine subjects who completed both experimental days with both doses of the two drugs. The intensity of global psychological effects was similar for DMT and (S)-ketamine. However, phenomena resembling positive symptoms of schizophrenia, particularly positive formal thought disorder and inappropriate affect, were stronger after DMT. Phenomena resembling negative symptoms of schizophrenia, attention deficits, body perception disturbances and catatonia-like motor phenomena were stronger after (S)-ketamine.

DISCUSSION:
The present study suggests that the NMDA antagonist model of psychosis is not overall superior to the serotonin 5-HT2A agonist model. Rather, the two classes of drugs tend to model different aspects or types of schizophrenia. The NMDA antagonist state may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5-HT2A agonist state may be a better model for psychoses of the paranoid type.

Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A., Stoll, M., Stock, C., Obradovic, M., & Kovar, K .A. (2005). Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry, 38(6), 301-311. http://dx.doi.org/10.1055/s-2005-916185
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Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine

November 4, 2004 / DMT, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

Abstract

The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT2A receptors play a pivotal role in the activity of hallucinogenic/ psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.

Jacob, M. S., & Presti, D. E. (2004). Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine. Medical Hypotheses, 64(5), 930-937. http://dx.doi.org/10.1016/j.mehy.2004.11.005

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Hallucinogens and dissociative agents naturally growing in the United States

May 1, 2004 / Ayahuasca, Cacti / Mescaline, DMT, Ethnobotany, Mushrooms / Psilocybin, Papers, Publications, Safety, Salvia / Salvinorin A, Toxicology / By /

Abstract

It is usually believed that drugs of abuse are smuggled into the United States or are clandestinely produced for illicit distribution. Less well known is that many hallucinogens and dissociative agents can be obtained from plants and fungi growing wild or in gardens. Some of these botanical sources can be located throughout the United States; others have a more narrow distribution. This article reviews plants containing N,N-dimethyltryptamine, reversible type A monoamine oxidase inhibitors (MAOI), lysergic acid amide, the anticholinergic drugs atropine and scopolamine, or the diterpene salvinorin-A (Salvia divinorum). Also reviewed are mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, and the Amanita muscaria and Amanita pantherina mushrooms that contain muscimol and ibotenic acid. Dangerous misidentification is most common with the mushrooms, but even a novice forager can quickly learn how to properly identify and prepare for ingestion many of these plants. Moreover, through the ever-expanding dissemination of information via the Internet, this knowledge is being obtained and acted upon by more and more individuals. This general overview includes information on the geographical range, drug content, preparation, intoxication, and the special health risks associated with some of these plants. Information is also offered on the unique issue of when bona fide religions use such plants as sacraments in the United States. In addition to the Native American Church’s (NAC) longstanding right to peyote, two religions of Brazilian origin, the Santo Daime and the Uniao do Vegetal (UDV), are seeking legal protection in the United States for their use of sacramental dimethyltryptamine-containing “ayahuasca.”

Halpern, J. H. (2004). Hallucinogens and dissociative agents naturally growing in the United States. Pharmacology & therapeutics, 102(2), 131-138. https://dx.doi.org/10.1016/j.pharmthera.2004.03.003
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DMT: The Spirit Molecule – A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences

February 6, 2022 / Boeken, Book reviews, DMT, Mystical experiences, Publicaties / By

spirit moleculeFrom 1990 to 1995 Dr. Rick Strassman conducted U.S. Government-approved and funded clinical research at the University of New Mexico in which he injected sixty volunteers with DMT, one of the most powerful psychedelics known. His detailed account of those sessions is an extraordinarily riveting inquiry into the nature of the human mind and the therapeutic potential of psychedelics. DMT, a plant-derived chemical found in the psychedelic Amazon brew, ayahuasca, is also manufactured by the human brain. In Strassman’s volunteers, it consistently produced near-death and mystical experiences. Many reported convincing encounters with intelligent nonhuman presences, aliens, angels, and spirits. Nearly all felt that the sessions were among the most profound experiences of their lives.

Strassman’s research connects DMT with the pineal gland, considered by Hindus to be the site of the seventh chakra and by René Descartes to be the seat of the soul. DMT: The Spirit Molecule makes the bold case that DMT, naturally released by the pineal gland, facilitates the soul’s movement in and out of the body and is an integral part of the birth and death experiences, as well as the highest states of meditation and even sexual transcendence. Strassman also believes that “alien abduction experiences” are brought on by accidental releases of DMT. If used wisely, DMT could trigger a period of remarkable progress in the scientific exploration of the most mystical regions of the human mind and soul.

Rick Strassman, M.D., is Clinical Associate Professor of Psychiatry at the University of New Mexico School of Medicine.

DMT: The Spirit Molecule, door Rick Strassman, Inner Traditions Bear and Company, 384 pagina’s.
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Pharmacokinetics of Hoasca alkaloids in healthy humans

June 1, 1999 / Ayahuasca, DMT, Ethnobotany, Indigenous use, Papers, Psychopharmacology, Publications / By / , , , , , ,

Abstract

N,N-Dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine (THH) are the characteristic alkaloids found in Amazonian sacraments known as hoasca, ayahuasca, and yajè. Such beverages are characterized by the presence of these three harmala alkaloids, where harmine and harmaline reversibly inhibit monoamine oxidase A (MAO-A) while tetrahydroharmine weakly inhibits the uptake of serotonin. Together, both actions increase central and peripheral serotonergic activity while facilitating the psychoactivity of DMT. Though the use of such ‘teas’ has be known to western science for over 100 years, little is known of their pharmacokinetics. In this study, hoasca was prepared and administered in a ceremonial context. All four alkaloids were measured in the tea and in the plasma of 15 volunteers, subsequent to the ingestion of 2 ml hoasca/kg body weight, using gas (GC) and high pressure liquid chromatographic (HPLC) methods. Pharmacokinetic parameters were calculated and peak times of psychoactivity coincided with high alkaloid concentrations, particularly DMT which had an average Tmax of 107.5±32.5 min. While DMT parameters correlated with those of harmine, THH showed a pharmacokinetic profile relatively independent of harmine’s.

Callaway, J. C., McKenna, D. J., Grob, C. S., Brito, G. S., Raymon, L. P., Poland, R. E., … & Mash, D. C. (1999). Pharmacokinetics of Hoasca alkaloids in healthy humans. Journal of ethnopharmacology, 65(3), 243-256. 10.1016/S0378-8741(98)00168-8
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Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness

January 1, 1999 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, LSD, Medicine, Mushrooms / Psilocybin, Mystical experiences, Papers, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By /

Abstract

Daily events that boost the immune system (as indicated by levels of salivary immunoglobulin A), some instances of spontaneous remission, and mystical experiences seem to share a similar cluster of thoughts, feelings, moods, perceptions, and behaviors. Entheogens – psychedelic drugs used in a religious context – can also produce mystical experiences (peak experiences, states of unitive consciousness, intense primary religious experiences) with the same cluster of effects. When this happens, is it also possible that such entheogen-induced mystical experiences strengthen the immune system? Might spontaneous remissions occur more frequently under such conditions? This article advances the so called “Emxis hypothesis” – that entheogen-induced mystical experiences influence the immune system.

Roberts, T. B. (1999). Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness. Advances in Mind-Body Medicine, 15, 139-147.
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Placeboing with Psychedelics

January 19, 1987 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Ketamine, LSD, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychology, Publications, Salvia / Salvinorin A / By /

Letter to the editor

When we consider the so-called “placebo effect,” we should realize that it is not something mysterious that merely happens on its own. It is something we do with our minds that effects our bodies. To be more accurate: we placebo. To placebo is a verb. Our minds plus our bodies do this, and like any other human activity we can speak of placeboing. When looked at this way, we can ask: How do we placebo? and Can we learn placeboing more skillfully?

A clue comes from studies of stress and emotions in the immune system. It is widely known that negative emotions and stressful life events weaken the immune system, while positive emotions and life events strengthen it. Since positive life events strengthen our immune system, here is a clue to learning to placebo.

A common healing cluster of positive feelings and thoughts accompany many instances of spontaneous remission and spiritual healing. These include feelings of exceedingly positive mood, being cared for in the hands of a loving power, dropping stress, feelings of sacredness, feeling at home in the world, among others. Thoughts include a sense of temporarily transcending one’s identity, forgiving oneself and others, overwhelming gratitude, and increased sense of reality—this is the way things really are and ought to be.

If we can reproduce this cluster, we will be on the way to learning to placebo. Various mindbody techniques including meditation, imagery, contemplative prayer, yoga, the martial arts, breathing techniques, hypnosis, and chanting all suggest a yes answer to this question, and more research to follow these apparent leads may lead to learning how to use these mindbody methods to increase our placeboing skills by strengthening our immune systems.

Do examples of extreme positive emotional states produce extreme healing? The recent flurry of articles about current research into exploring the psychotherapeutic use of psychedelics for post traumatic stress disorder, death anxiety, and other disorders show that these substances are successful when they produce states of unitive consciousness (mystical experiences) and not successful when they do not.

Lost in this discussion is that fact that mystical experiences are the most powerful emotionally positive experiences humans can have, and if normal daily positive events boost the immune system somewhat, do these strongest positive experiences boost it a great deal?

Can this spontaneous cluster of healing thoughts and feelings be recreated in a medical setting? As a 2008 Johns Hopkins study of psilocybin induced mystical experiences showed, under the right conditions and with careful screening, preparation, and professional guidance, psychedelic sessions can produce mystical experiences and a similar cluster of emotions and experiences in normal, healthy, adult volunteers. In a 14-month following up, volunteers’ comments illustrated this healing cluster:

– The utter joy and freedom of letting go—without anxiety—without direction— beyond ego self.
– The understanding that in the eyes of God—all people—were equally important and equally loved by God.
– When I confronted my shadow and yelled “What do you want?” and it disappeared in a puff smoke.

Among the other outcomes were positive mood changes, improved sense of well-being and life satisfaction, positive attitudes about life and/or self, and altruistic social effects. About two-thirds of healthy adults rated as one of the five most important spiritual experiences of their lives, including about one-third who rated them as the single most important spiritual experience of their lives. However, the researchers did not measure possible effects on the immune system.

A question on placeboing: Do overwhelmingly powerful peak experiences stimulated by psychedelics as part of professionally guided sessions boost the immune system? A possible major advance in mindbody health awaits an answer.

Roberts, T. B. (1987). Is There a Placebo Ability? Advances: Journal of the Institute for the Advancement of Health, 4(1), 5.

30 April - Q&A with Rick Strassman

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