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The behavioral pharmacology of hallucinogens

/ DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / / , ,

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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Ayahuasca and Anthropology: Amazonian Shamanism & Western Science

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In this lecture at the University of Amsterdam on Monday December 17th 2007, Arno Adelaars introduced ayahuasca to those unfamiliar with the substance, after which Jeremy Narby filled the rest of the time. He spoke about ayahuasca and his experiences with the Ashaninca in the Peruvian Amazon.

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Comparative potencies of MDMA analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines

/ MDMA, Papers, Pharmacology & Chemistry, Publications / / , , , , ,

Abstract

Background and purpose:Illegal ‘ecstasy’ tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [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”][3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT).

Experimental approach:Concentration–response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy 3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl- N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA).

Key results: 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT.

Conclusions and implications: This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.

Montgomery, T., Buon, C., Eibauer, S., Guiry, P. J., Keenan, A.K., & McBean, G. J. (2007). Comparative potencies of MDMA analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. British Journal of Pharmacology, 152(7), 1121–1130. http://dx.doi.org/10.1038/sj.bjp.0707473
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Chronic Phenethylamine Hallucinogen Treatment Alters Behavioral Sensitivity to a Metabotropic Glutamate 2/3 Receptor Agonist

/ Papers, Psychotic Disorders, Publications / / , ,

Abstract

Recent clinical studies in schizophrenic patients show that a selective agonist of group II metabotropic glutamate (mGlu) receptors has robust efficacy in treating positive and negative symptoms. Group II mGlu receptor agonists also modulate the in vivo activity of psychotomimetic drugs, reducing the ability of psychotomimetic hallucinogens to increase glutamatergic transmission. The use of mouse models provides an opportunity to investigate the dynamic action that mGlu2/3 receptors play in regulating the behavioral effects of hallucinogen-induced glutamatergic neurotransmission using genetic as well as pharmacological strategies. The current study sought to characterize the use of the two-lever drug discrimination paradigm in ICR (CD-1) mice, using the hallucinogenic 5-HT2A/2C receptor agonist (−)-2,5-dimethoxy-4-bromoamphetamine [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”][(−)-DOB)] as a stimulus-producing drug. The (−)-DOB discriminative stimulus was dose-dependent, generalized to the hallucinogen lysergic acid diethylamide, and was potently blocked by the 5-HT2A receptor antagonist M100907. However, contrary to our prediction, the hallucinogen-induced discriminative stimulus was not regulated by mGlu2/3 receptors. In a series of follow-up studies using hallucinogen-induced head twitch response and phencyclidine-induced hyperlocomotion, it was additionally discovered that the repeated dosing regimen required for discrimination training attenuated the behavioral effects of the mGlu2/3 receptor agonist LY379268. Furthermore chronic studies, using a 14 day (−)-DOB treatment, confirmed that repeated hallucinogen treatment causes a loss of behavioral activity of mGlu2/3 receptors, likely resulting from persistent activation of mGlu2/3 receptors by a hallucinogen-induced hyperglutamatergic state.

Benneyworth, M. A., Smith, R. L., & Sanders-Bush, E. (2008). Chronic Phenethylamine Hallucinogen Treatment Alters Behavioral Sensitivity to a Metabotropic Glutamate 2/3 Receptor Agonist. Neuropsychopharmacology, 33, 2206–2216. http://dx.doi.org/10.1038/sj.npp.1301600
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Land of the Living Sky with Diamonds: A Place for Radical Psychiatry?

/ LSD, Papers, Publications / /

Abstract

Dr. Humphry Osmond first published the term “psychedelic” in 1957 as a result of an extensive set of clinical investigations with d-lysergic acid diethylmide (LSD) that took place in Saskatchewan in the 1950s. In the post-World War Two period, Saskatchewan became an attractive destination for medical, and in this case psychiatric, researchers who wanted to pursue theoretical and practical investigations that challenged disciplinary boundaries and critically examined the relationship between medicine and the state. Partly as a result of Saskatchewan’s post-war political culture, the province became an intellectual sanctuary for medical experimentation that in some other contexts did not gain currency because it appeared too radical. This essay examines the way that psychedelic psychiatry emerged in that province and argues that the social, cultural and political environment in post-war Saskatchewan played a significant role in attracting researchers and supporting LSD research.

Dyck, E. (2007). Land of the living sky with diamonds: A place for radical psychiatry?. Journal of Canadian Studies/Revue d’études canadiennes, 41(3), 42-66.
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Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

/ Mushrooms / Psilocybin, Neuroscience, Papers, Publications / / , , , , ,

Abstract

Rationale: Binocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psychosis.

Objectives: The objective of the study was to explore the proposed relationship between binocular rivalry switch rate and subjective changes in psychological state associated with 5-HT2A receptor activation.

Materials and methods: This study used psilocybin, the hallucinogen found naturally in Psilocybe mushrooms that had previously been found to induce psychosis-like symptoms via the 5-HT2A receptor. The effects of psilocybin (215 μg/kg) were considered alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy human subjects.

Results: Psilocybin significantly reduced the rate of binocular rivalry switching and increased the proportion of transitional/mixed percept experience. Pretreatment with ketanserin blocked the majority of psilocybin’s “positive” psychosis-like hallucinogenic symptoms. However, ketanserin had no influence on either the psilocybin-induced slowing of binocular rivalry or the drug’s “negative-type symptoms” associated with reduced arousal and vigilance.

Conclusions: Together, these findings link changes in binocular rivalry switching rate to subjective levels of arousal and attention. In addition, it suggests that psilocybin’s effect on binocular rivalry is unlikely to be mediated by the 5-HT2A receptor.

Carter, O. L., Hasler, F., Pettigrew, J. D., Wallis, G. M., Liu, G. B., & Vollenweider, F. X. (2007). Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans. Psychopharmacology, 195(3), 415-424. 10.1007/s00213-007-0930-9

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Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members

/ Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / / , , , ,

Abstract

The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1 h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.

Santos, R. G., Landeira-Fernandez, J., Strassman, R. J., Motta, V., & Cruz, A. P. M. (2007). Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. Journal of Ethnopharmacology, 112(3), 507-513. http://dx.doi.org/10.1016/j.jep.2007.04.012
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Psychedelic Medicine: New Evidence for Hallucinogenic Substances as Treatments

/ Publications /

51qUsAI+YsL._SX327_BO1,204,203,200_Psychedelic substances present in nature have been used by humans across hundreds of years to produce mind-altering changes in thought, mood, and perception―changes we do not experience otherwise except rarely in dreams, religious exaltation, or psychosis. U.S. scientists were studying the practical and therapeutic uses for hallucinogens, including LSD and mescaline, in the 1950s and 1960s supplied by large manufacturers including Sandoz. But the government took steps to ban all human consumption of hallucinogens, and thus the research. By the 1970s, all human testing was stopped. Medical concerns were not the issue, the ban was motivated by social concerns, not the least of which were created by legendary researcher Timothy Leary, a psychologist who advocated free use of hallucinogens by all who desired. Nationwide, however, a cadre of scholars and researchers has persisted in pushing the federal government to again allow human testing and the moratorium has been lifted. The FDA has begun approving hallucinogenic research using human subjects. In these groundbreaking volumes, top researchers explain the testing and research underway to use―under the guidance of a trained provider―psychedelic substances for better physical and mental health.

Psychedelic Medicine: New Evidence for Hallucinogenic Substances as Treatments [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”][2 delen], door Thomas B. Roberts & Michael J. Winkelman, Praeger Perspectives reeks, Praeger, 728 pagina’s.

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Psilocybin-induced stimulus control in the rat

/ Mushrooms / Psilocybin, Neuroscience, Papers, Publications / / , , ,

Abstract

Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT1A/7 receptor antagonist, WAY-100635, or the DA D2 antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT2A receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT1A receptors appears to play no role in psilocybin-induced stimulus control.

Winter, J. C., Rice, K. C., Amorosi, D. J., & Rabin, R. A. (2007). Psilocybin-induced stimulus control in the rat. Pharmacology Biochemistry and Behavior, 87(4), 472-480. http://dx.doi.org/10.1016/j.pbb.2007.06.003
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Brave New World versus Island — Utopian and Dystopian Views on Psychopharmacology

/ Papers, Philosophy & Religious Studies, Publications / /

Abstract

Aldous Huxley’s Brave New World is a famous dystopia, frequently called upon in public discussions about new biotechnology. It is less well known that 30 years later Huxley also wrote a utopian novel, called Island. This paper will discuss both novels focussing especially on the role of psychopharmacological substances. If we see fiction as a way of imagining what the world could look like, then what can we learn from Huxley’s novels about psychopharmacology and how does that relate to the discussion in the ethical and philosophical literature on this subject? The paper argues that in the current ethical discussion the dystopian vision on psychopharmacology is dominant, but that a comparison between Brave New World and Island shows that a more utopian view is possible as well. This is illustrated by a discussion of the issue of psychopharmacology and authenticity. The second part of the paper draws some further conclusions for the ethical debate on psychopharmacology and human enhancement, by comparing the novels not only with each other, but also with our present reality. It is claimed that the debate should not get stuck in an opposition of dystopian and utopian views, but should address important issues that demand attention in our real world: those of evaluation and governance of enhancing psychopharmacological substances in democratic, pluralistic societies.

Schermer, M. H. N. (2007). Brave New World versus Island—Utopian and Dystopian Views on Psychopharmacology. Medicine, Health Care and Philosophy, 10(2), 119-128. https://dx.doi.org/10.1007/s11019-007-9059-1

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Peer Perspectives: Psychedelic Work at the End of Life — The Inner World of the Dying & the Practice of Guiding - Aug 27

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