OPEN Foundation

Mescaline / Cacti

Serotonin-Related Psychedelic Drugs

Abstract

Serotonergic hallucinogens include the prototypical compounds such as mescaline, psilocybin, and LSD, representing the chemical classes of phenethylamines, tryptamines, and ergolines. Known as psychedelics, these compounds induce dramatic alterations of perception, affect, consciousness, and the experience of self. As first discovered in animal studies and recently confirmed in humans, the psychological effects of psychedelics are primarily attributable to the activation of the 5-HT2A subtype of serotonin receptors in brain. Research on psychedelic compounds has provided important insights into the neurobiology of consciousness and naturally occurring psychotic states and may lead to further advances in the development of psychiatric pharmacotherapeutics.

Geyer, M. A., Nichols, D. E., & Vollenweider, F. X. (2009). Serotonin-related psychedelic drugs. 10.1016/B978-008045046-9.01160-8
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Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines

Abstract

Background: Although man’s first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species.

Objective: The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine.

Results: The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT2A receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT2C and 5-HT1A receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities.

Conclusions: Hallucinogen-induced stimulus control provides a unique behavioral tool for the prediction of subjective effects in man and for the elucidation of the pharmacological mechanisms of the action of these agents.

Winter, J. C. (2009). Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines. Psychopharmacology, 203(2), 251–263. http://dx.doi.org/10.1007/s00213-008-1356-8
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Human hallucinogen research: guidelines for safety

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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The behavioral pharmacology of hallucinogens

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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Effects of mescaline and lysergic acid (d-LSD-25)

The effects of mescaline and lysergic acid were studied in schizophrenic patients. It was found that physiological changes were produced in these patients and that their mental symptomatology was markedly aggravated. The observations made with the above-mentioned drugs on normal individuals were compared with those seen in schizophrenic patients. Mescaline and lysergic acid are drugs that disorganize the psychic integration of a person. This disorganization is much more apparent in schizophrenics than in normals. The diagnostic, prognostic, and therapeutic use of these drugs is also discussed.

Hoch, P. H., Cattell, J. P., & Pennes, H. H. (1952). Effects of mescaline and lysergic acid (d-LSD-25). American Journal of Psychiatry108(8), 579-584.,10.1176/ajp.108.8.579

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Hallucinogenic botanicals of America: A growing need for focused drug education and research

Abstract

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.

Halpern, J. H., & Sewell, R. A. (2005). Hallucinogenic botanicals of America: A growing need for focused drug education and research. Life sciences, 78(5), 519-526. https://dx.doi.org/10.1016/j.lfs.2005.09.005
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Hallucinogens and dissociative agents naturally growing in the United States

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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Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness

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

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.

Psychedelic Agents in Creative Problem-Solving: A Pilot Study

Abstract

Based on the frequently reported similarities between creative and psychedelic (drug-induced, consciousness-expansion) experiences, a preliminary study was conducted to explore the effects of psychedelic agents (LSD-25, mescaline) on creative problem-solving ability. Twenty-seven professionally employed males were given a single psychedelic experience in 1 of 7 small groups (ns = 3 or 4) following extensive selection and preparatory procedures. This drug-induced problem-solving session was carefully structured with particular focus on establishing Ss’ expectancies and a psychosocial milieu conducive to creative activity. Tentative findings based on tests of creativity, on subjective reports and self ratings, and on the utility of problem solutions suggested that, if given according to this carefully structured regimen, psychedelic agents seem to facilitate creative problem-solving, particularly in the “illumination phase.” The results also suggest that various degrees of increased creative ability may continue for at least some weeks subsequent to a psychedelic problem-solving session.

Harman, W. W., McKim, R. H., Mogar, R. E., Fadiman, J., & Stolaroff, M. J. (1966). Psychedelic Agents in Creative Problem-Solving: A Pilot Study. Psychological Reports, 19, 211-227.
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