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Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

/ Ayahuasca, DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / ,

Abstract

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors.

Halberstadt, A. L., & Geyer, M.A. (2011). Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 61(3), 364-381. http://dx.doi.org/10.1016/j.neuropharm.2011.01.017
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Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer

/ Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , , , ,

Abstract

Context: Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer.

Objective: To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety.

Design: A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin.

Setting: A clinical research unit within a large public sector academic medical center.

Participants: Twelve adults with advanced-stage cancer and anxiety.

Main Outcome Measures: In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment.

Results: Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance.

Conclusions: This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field.

Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer. Archives of General Psychiatry, 68(1), 71-78. http://dx.doi.org/10.1001/archgenpsychiatry.2010.116
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Characterization of behavioral and endocrine effects of LSD on zebrafish

/ LSD, Papers, Publications / / , , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light–dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5–100 μg/L) did not affect zebrafish behavior, 250 μg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light–dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse.

Grossman, L., Utterback, E., Stewarta, A., Gaikwada, S., Chunga, K. M., Suciua, C., … Kalueff, A. V. (2010). Characterization of behavioral and endocrine effects of LSD on zebrafish. Behavioural Brain Research, 214(2), 277-284. http://dx.doi.org/10.1016/j.bbr.2010.05.039
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Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others

/ MDMA, Papers, Psychology, Publications / / , ,

Abstract

Background: Users of MDMA (“ecstasy”) report that the drug produces unusual psychological effects, including increased empathy and prosocial feelings. These “empathogenic” effects are cited as reasons for recreational ecstasy use and also form the basis for the proposed use of MDMA in psychotherapy. However, they have yet to be characterized in controlled studies. Here, we investigate effects of MDMA on an important social cognitive capacity, the identification of emotional expression in others, and on socially relevant mood states.

Methods: Over four sessions, healthy ecstasy-using volunteers (n = 21) received MDMA (.75, 1.5 mg/kg), methamphetamine (METH) (20 mg), and placebo under double-blind, randomized conditions. They completed self-report ratings of relevant affective states and undertook tasks in which they identified emotions from images of faces, pictures of eyes, and vocal cues.

Results: MDMA (1.5 mg/kg) significantly increased ratings of feeling “loving” and “friendly”, and MDMA (.75 mg/kg) increased “loneliness”. Both MDMA (1.5 mg/kg) and METH increased “playfulness”; only METH increased “sociability”. MDMA (1.5 mg/kg) robustly decreased accuracy of facial fear recognition relative to placebo.

Conclusion: The drug MDMA increased “empathogenic” feelings but reduced accurate identification of threat-related facial emotional signals in others, findings consistent with increased social approach behavior rather than empathy. This effect of MDMA on social cognition has implications for both recreational and therapeutic use. In recreational users, acute drug effects might alter social risk-taking while intoxicated. Socioemotional processing alterations such as those documented here might underlie possible psychotherapeutic benefits of this drug; further investigation of such mechanisms could inform treatment design to maximize active components of MDMA-assisted psychotherapy.

Bedia, G., Hymana, D., & de Wit, H. (2010). Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others. Biological Psychiatry, 68(12), 1134-1140. http://dx.doi.org/10.1016/j.biopsych.2010.08.003
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Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial

/ Papers, Publications, Salvia / Salvinorin A / / , , , , , ,

Abstract

Rationale: Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.

Objectives: The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.

Methods: Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design.

Results: No dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported “typical” effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL).

Cconclusions: Our results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.

Mendelson, J. E., Coyle, J. R., Lopez, J.C., Baggott, M. J., Flower, K., Everhart, E. T., … Cohen, B. M. (2010). Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial. Psychopharmacology, 214(4), 933-939. http://dx.doi.org/10.1007/s00213-010-2103-5
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Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans

/ Papers, Psychology, Publications / / , , , , ,

Abstract

Background: The mechanisms of drug-induced visions are poorly understood. Very few serotonergic hallucinogens have been studied in humans in decades, despite widespread use of these drugs and potential relevance of their mechanisms to hallucinations occurring in psychiatric and neurological disorders.

Methodology/Principal Findings: We investigated the mechanisms of hallucinogen-induced visions by measuring the visual and perceptual effects of the hallucinogenic serotonin 5-HT2AR receptor agonist and monoamine releaser, 3,4-methylenedioxyamphetamine (MDA), in a double-blind placebo-controlled study. We found that MDA increased self-report measures of mystical-type experience and other hallucinogen-like effects, including reported visual alterations. MDA produced a significant increase in closed-eye visions (CEVs), with considerable individual variation. Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition.

Conclusions/Significance: Drug-induced visions may have greater intensity in people with poor sensory or perceptual processing, suggesting common mechanisms with other hallucinatory syndromes. MDA is a potential tool to investigate mystical experiences and visual perception.

Baggott, M. J., Siegrist, J. D., Galloway, G. P., Robertson, L. C., Coyle, J. R., & Mendelson, J. E. (2010). Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans. PLoS ONE, 5(12), 1-13. http://dx.doi.org/10.1371/journal.pone.0014074
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Evolution and origins of the Mazatec hallucinogenic sage, Salvia divinorum (Lamiaceae): a molecular phylogenetic approach

/ Biology & Ethnobotany, Papers, Publications, Salvia / Salvinorin A / / , ,

Abstract

Salvia divinorum Epl. & Játiva-M. (Lamiaceae) is a potent hallucinogenic plant that is classified within Salvia subgenus Calosphace, section Dusenostachys, and hypothesized to be an interspecific hybrid. It is of ethnobotanical significance due to its employment in traditional healing ceremonies by the Mazatecs of Oaxaca, Mexico, and due to its unique pharmacology—a highly selective, non-nitrogenous, j-opioid receptor agonist. In order to test its phylogenetic position and putative hybridity, we sequenced multiple DNA regions (ITS, trnL-trnF, and psbA-trnH) of 52 species—representing the major lineages of subgenus Calosphace—and six accessions of S. divinorum. Our molecular phylogenetic results suggest that S. divinorum should not be classified within Dusenostachys and that it is not a hybrid. Additionally, we determine that the closest known relative of this psychoactive Mexican sage is S. venulosa, a rare endemic of Colombia.

Jenks, A. A., Walker, J.B., Kim, S. C. (2010). Evolution and origins of the Mazatec hallucinogenic sage, Salvia divinorum (Lamiaceae): a molecular phylogenetic approach. Journal of Plant Research, 124(5), 593-600. http://dx.doi.org/10.1007/s10265-010-0394-6
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Ayahuasca, Salutogenesis and the Need for „Ecological“ Approaches

/ Ayahuasca, Papers, Publications / /

Abstract

In Western science, extraordinary or visionary states of consciousness are traditionally discussed mainly in terms of psychopathology, that is, in the sense of mental disease. This applies even more when they are associated with psychoactive substances such as the herbal decoction Ayahuasca, which are generally called “hallucinogens” with the connotation “not objective, unreal”. However, responsible work with psychoactive herbal decoctions like Ayahuasca – similar to many forms of meditation – has salutogenic potential, i.e. it can enhance physical, mental and spiritual health by calling into play what is referred to as “participating consciousness”. Rigid feeling, thought, and behavioural patterns can unclench, the self can rearrange itself and develop its inner and outer resources more deeply.

The thesis of this article is that for an adequate understanding of these processes, the familiar “linear” thinking no longer suffices, rather, an “ecology of mind” is needed (Bateson 1972), i.e. less divisive, less objectifying explanations which also do not exclude the fundamental paradoxes of human existence. Of course, such approaches occasionally need some getting used to.

In the following, a few basic elements of the ecological approach will be explained (chapter 2). Chapter 3 will then analyze whether or not and to what extent this approach can explain extraordinary states of consciousness better than traditional, linear thinking.

Friczewski, F. (2010). Ayahuasca, Salutogenesis and the Need for „Ecological“ Approaches.

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