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Psychopharmacology

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

September 14, 2007 / Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychiatry, Psychopharmacology, Publications / By / , , , , ,

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

July 27, 2007 / Anxiety disorders / PTSD, Ayahuasca, Depression, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Safety / By / , , , ,

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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Psilocybin-induced stimulus control in the rat

June 22, 2007 / Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychopharmacology, Publications / By / , , ,

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

May 8, 2007 / Other disciplines, Other subjects, Other substances, Papers, Philosophy, Psychopharmacology, Publications, Sociology / By /

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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Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior.

February 1, 2007 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural circuits mediate their effects are poorly understood. By genetically expressing 2AR only in cortex, we show that 2AR-regulated pathways on cortical neurons are sufficient to mediate the signaling pattern and behavioral response to hallucinogens. Hallucinogenic and nonhallucinogenic 2AR agonists both regulate signaling in the same 2AR-expressing cortical neurons. However, the signaling and behavioral responses to the hallucinogens are distinct. While lisuride and LSD both act at 2AR expressed by cortex neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric G(i/o) proteins and Src. These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens.

González-Maeso, J., Weisstaub, N. V., Zhou, M., Chan, P., Ivic, L., Ang, R., … & Gingrich, J. A. (2007). Hallucinogens recruit specific cortical 5-HT 2A receptor-mediated signaling pathways to affect behavior. Neuron, 53(3), 439-452.  http://dx.doi.org/10.1016/j.neuron.2007.01.008

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Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder

November 11, 2006 / Anxiety disorders / PTSD, Mushrooms / Psilocybin, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety / By / , , ,

Abstract

Background: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD.

Method: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004.

Results: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint.

Conclusion: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.
Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Journal of Clinical Psychiatry, 67(11), 1735-1740.

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Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

July 7, 2006 / Mushrooms / Psilocybin, Mystical experiences, Papers, Personal development, Psychology, Psychopharmacology, Publications, Spirituality / By / , ,

Abstract

Rationale: Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects.

Objectives: This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions.

Materials and methods: The participants were hallucinogennaïve adults reporting regular participation in religious orspiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers’ behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer’s attitudes and behavior.

Results: Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers.

Conclusions: When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.

Griffiths, R. R., Richards, W. A., & McCann, U. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268–283. http://dx.doi.org/10.1007/s00213-006-0457-5
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Effects of mescaline and lysergic acid (d-LSD-25)

April 6, 2006 / Anxiety disorders / PTSD, Cacti / Mescaline, LSD, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

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 Psychiatry, 108(8), 579-584.,10.1176/ajp.108.8.579

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Mechanisms of antiaddictive actions of ibogaine

February 7, 2006 / Addiction, Iboga / Ibogaine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

Abstract

Ibogaine, an alkaloid extracted from Tabemanthe iboga, is being studied as a potential long-acting treatment for oploid and stimulant abuse as well as for alcoholism and smoking. Studies in this laboratory have used animal models to characterize ibogaine’s interactions with drugs of abuse, and to investigate the mechanisms responsible. Ibogaine, as well as its metabolite, noribogaine, can decrease both morphine and cocaine self-administration for several days in some rats; shorter-lasting effects appear to occur on ethanol and nicotine intake. Acutely, both ibogaine and noribogaine decrease extracellular levels of dopamine in the nucleus accumbens of rat brain. Ibogaine pretreatment (19 hours beforehand) blocks morphine-induced dopamine release and morphine-induced locomotor hyperactivity while, in contrast, it enhances similar effects of stimulants (cocaine and amphetamine). Ibogaine pretreatment also blocks nicotine-induced dopamine release. Both ibogaine and noribogaine bind to kappa opioid and N-methyl-D-aspartate (NMDA) receptors and to serotonin uptake sites; ibogaine also binds to sigma-2 and nicotinic receptors. The relative contributions of these actions are being assessed. Our ongoing studies in rats suggest that kappa agonist and NMDA antagonist actions contribute to ibogaine’s effects on opioid and stimulant self-administration, while the serotonergic actions may be more important for ibogaine-induced decreases in alcohol intake. A nicotinic antagonist action may mediate ibogaine-induced reduction of nicotine preferences in rats. A sigma-2 action of ibogaine appears to mediate its neurotoxicity. Some effects of ibogaine (e.g., on morphine and cocaine self-administration, morphine-induced hyperactivity, cocaine-induced increases in nucleus accumbens dopamine) are mimicked by kappa agonist (U50,488) and/or a NMDA antagonist (MK-801). Moreover, a combination of a kappa antagonist and a NMDA agonist will partially reverse several of ibogaine’s effects. Ibogaine’s long-term effects may be mediated by slow release from fat tissue (where ibogaine is sequestered) and conversion to noribogaine. Different receptors, or combinations of receptors, may mediate interactions of ibogaine with different drugs of abuse.

Glick, S. D., & Maisonneuve, I. S. (1998). Mechanisms of antiaddictive actions of ibogaine. Annals of the New York Academy of Sciences, 844, 214-226. http://dx.doi.org/10.1111/j.1749-6632.1998.tb08237.x
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Screening the receptorome for plant-based psychoactive compounds

December 22, 2005 / Ayahuasca, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By / ,

Abstract

Throughout time, humans have used psychoactive plants and plant-derived products for spiritual, therapeutic and recreational purposes. Furthermore, the investigation of psychoactive plants such as Cannabis sativa (marijuana), Nicotiana tabacum (tobacco) and analogues of psychoactive plant derivatives such as lysergic acid diethylamide (LSD) have provided insight into our understanding of neurochemical processes and diseases of the CNS. Currently, many of these compounds are being used to treat a variety of diseases, such as depression and anxiety in the case of Piper methysticum Kava Kava (Martin et al., 2002; Singh and Singh, 2002). G-protein coupled receptors (GPCRs) are the most common molecular target for both psychoactive drugs and pharmaceuticals. The “receptorome” (that portion of the genome encoding ligand reception) encompasses more than 8% of the human genome (Roth et al., 2004) and as such provides a large number of possible targets for psychoactive drug interactions. A systematic, comprehensive study is necessary to identify novel active psychoactive plant-based compounds and the molecular targets of known compounds. Herein we describe the development of a high throughput system (HTS) to screen psychoactive compounds against the receptorome and present two examples (Salvia divinorum, the “magic mint” hallucinogen and Banisteriopsis caapi, the main component of Ayahuasca, a psychoactive beverage) where HTS enabled the identification of the molecular target of each compound.

O’connor, K. A., & Roth, B. L. (2005). Screening the receptorome for plant-based psychoactive compounds. Life sciences, 78(5), 506-511. 10.1016/j.lfs.2005.09.002
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7 May - Psychedelics, Nature & Mental Health with Sam Gandy

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