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LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study.

Abstract

A pilot open study was conducted in order to evaluate the efficacy of clonidine in the treatment of LSD-induced hallucinogen persisting perception disorder (HPPD). Eight patients fulfilled entrance criteria. All complained of HPPD for at least 3 months and were drug free at least 3 months. They received fixed low doses of clonidine, 0.025 mg, three times a day for 2 months. They were evaluated by the Clinical Global Impression Scale (CGI) and a self-report scale on the severity of symptoms (graded 0-5). Patients scored an average of 5.25 (SD = 0.46) on the CGI and 4 on the self-report scale at baseline, indicating marked psychopathology. One patient dropped out at week 3 and a second patient dropped out at week 5. Of the six patients remaining at the end of 2 months, the average CGI score was 2.5 (SD = 0.55) and the self-report scale score was 2, indicating mild symptomatology. LSD-related flashbacks associated with excessive sympathetic nervous activity may be alleviated with clonidine in some patients.

Lerner, A. G., Gelkopf, M., Oyffe, I., Finkel, B., Katz, S., Sigal, M., & Weizman, A. (2000). LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study. International clinical psychopharmacology, 15(1), 35-37.
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Role of Serotoninergic Neurons and 5-HT Receptors in the Action of Hallucinogens

Abstract

Brain serotonin receptors and serotoninergic pathways have received increasing attention as targets for a wide variety of therapeutic agents. Perhaps peculiar to this realm, however, are the so-called hallucinogenic drugs, which presently lack demonstrated therapeutic utility, and still remain, as they have for at least the past 50 years, pharmacological curiosities. Research into their mechanism of action is generally poorly funded, and we know relatively little about how they affect the brain, despite their continued popularity as recreational drugs among a significant proportion of the population.

Nichols, D. E. (2000). Role of serotoninergic neurons and 5-HT receptors in the action of hallucinogens. In Serotoninergic Neurons and 5-HT Receptors in the CNS (pp. 563-585). Springer Berlin Heidelberg. http://dx.doi.org/10.1007/978-3-642-60921-3_21

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Pharmacokinetics of Hoasca alkaloids in healthy humans

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

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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Psilocybin induces schizophrenia‐like psychosis in humans via a serotonin‐2 agonist action

Abstract

Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Bäbler, A., Vogel, H., & Hell, D. (1998). Psilocybin induces schizophrenia‐like psychosis in humans via a serotonin‐2 agonist action. Neuroreport, 9(17), 3897-3902. https://dx.doi.org/doi:10.1097/00001756-199812010-00024
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Ketamine psychedelic therapy (KPT): a review of the results of ten years of research

Abstract

Ketamine is a prescription drug used for general anesthesia. In subanesthetic doses, it induces profound psychedelic experiences and hallucinations. The subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in the authors’ use of ketamine-assisted psychotherapy for alcoholism. The results of a controlled clinical trial demonstrated a considerable increase in efficacy of the authors’ standard alcoholism treatment when supplemented by ketamine psychedelic therapy (KPT). Total abstinence for more than one year was observed in 73 out of 111 (65.8%) alcoholic patients in the KPT group, compared to 24% (24 out of 100 patients) of the conventional treatment control group (p < 0.01). The authors’ studies of the underlying psychological mechanisms of KPT have indicated that ketamine-assisted psychedelic therapy of alcoholic patients induces a harmonization of the Minnesota Multiphasic Personality Inventory (MMPI) personality profile, positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to various aspects of self and other people, positive changes in life values and purposes, important insights into the meaning of life and an increase in the level of spiritual development. Most importantly, these psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations showed that pharmacological action of KPT affects both monoaminergic and opioidergic neurotransmitter metabolism, i.e., those neurochemical systems which are involved in the pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis demonstrated that ketamine increases theta activity in cerebrocortical regions of alcoholic patients. This is evidence of the reinforcement of limbic cortex interaction during KPT session.

Krupitsky, E. M., & Grinenko, A. Y. (1997). Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. Journal of psychoactive drugs, 29(2), 165-183. https://dx.doi.org/10.1080/02791072.1997.10400185

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Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis

Abstract

The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [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”][F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin.

Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metabolic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.

Vollenweider, F. X., Leenders, K. L., Scharfetter, C., Maguire, P., Stadelmann, O., & Angst, J. (1997). Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology, 16(5), 357-372. http://dx.doi.org/10.1016/S0893-133X(96)00246-1
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Increased Activation of Indirect Semantic Associations under Psilocybin

Abstract

The spread of activation in semantic networks can be measured using semantic and indirect semantic priming effects in lexical decision tasks (Spitzer et al 1993a and b). For example, in thought-disordered schizophrenic patients, activation spreads faster and farther than in non-thought-disordered patients and normal subjects, which results in an increased direct and indirect semantic priming effect (see below). This has been interpreted as the result of a decreased signal-to-noise ratio in cortical neural networks that process semantic information. Such a decreased signal-to-noise ratio has been related to a decreased dopaminergic modulation (Servan-Schreiber et al. 1990; Cohen and Servan- Schreiber 1992, 1993), which we recently were able to confirm directly in a study on the effects of L-dopa on semantic and indirect semantic priming (Kischka et al 1995).

As dopamine was found to have a focusing effect on the activity in semantic networks, i.e., it increases the signal-to-noise ratio and reduces the spread of activation (measured as reduced indirect semantic priming), we set out to investigate the effect of the hallucinogenic agent psilocybin on this task. Since psilocybin is known to act on the serotonin (5-HT) system and has effects of “broadening” conscious experiences, we hypothesized that it might exert a defocusing effect on semantic networks (i.e., decrease the signal-to-noise ratio), which should lead to an increased indirect semantic priming effect.

To test this hypothesis directly, we conducted a double-blind, placebo-controlled study on the effects of psilocybin on semantic and indirect semantic priming as part of a larger project that was designed to assess the behavioral effects and pharmacokinetic properties of this hallucinogenic agent (the results will be reported elsewhere; cf. Holzmann 1995).

Spitzer, M., Thimm, M., Hermle, L., Holzmann, P., Kovar, K., Heirnann, H., … Schneider, F. (1996). Increased Activation of Indirect Semantic Associations under Psilocybin. Biological Psychiatry, 39(12),  1055–1057. http://dx.doi.org/10.1016/0006-3223(95)00418-1
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The psychopharmacology of hallucinogens.

Abstract

Hallucinogenic drugs have been inhaled, ingested, worshipped, and reviled since prehistory. With the purification and synthesis of bontanical preparations and the ensuing discovery of chemically unique agents, hope was raised regarding their therapeutic potential, but this hope has been clouded by an epidemic of abuse and an inventory of adverse effects. This review examines aspects of that controversy, including the history of hallucinogens, epidemiology of current hallucinogen abuse, the association of LSD use with prolonged psychoses and hallucinogen persisting perception disorder, and the efforts to demonstrate the drug’s therapeutic efficacy. Human subject ramifications in hallucinogen experimentation are discussed. Future lines of research are suggested in human, animal, and tissue culture paradigms.

Abraham, H. D., Aldridge, A. M., & Gogia, P. (1996). The psychopharmacology of hallucinogens. Neuropsychopharmacology, 14(4), 285-298. https://dx.doi.org/10.1016/0893-133X(95)00136-2
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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.

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