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Mushrooms / Psilocybin

Effects of varied doses of psilocybin on time interval reproduction in human subjects

April 11, 2008 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5 s. The effects were assessed by parameter κκ of the ‘dual klepsydra’ model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates View the MathML sourceκˆ were in the same order of magnitude as in earlier studies. In both experiments, κκ was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

Wackermann, J., Wittmann, M., Hasler, F., & Vollenweider, F. X. (2008). Effects of varied doses of psilocybin on time interval reproduction in human subjects. Neuroscience letters, 435(1), 51-55. https://dx.doi.org/10.1016/j.neulet.2008.02.006
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The behavioral pharmacology of hallucinogens

January 1, 2008 / DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / By / , ,

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

September 14, 2007 / Mushrooms / Psilocybin, Neuroscience, Papers, 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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Psilocybin-induced stimulus control in the rat

June 22, 2007 / Mushrooms / Psilocybin, Neuroscience, Papers, 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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The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval

February 14, 2007 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , ,

Abstract

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT2A receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT2A receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 mug/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120–2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

Vollenweider, F. X, Csomor, P. A., Knappe, B., Geyer, M. A., & Quednow, B. B. (2007). The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval. Neuropsychopharmacology, 32(9), 1876-1887. http://dx.doi.org/10.1038/sj.npp.1301324
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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, Psychology, 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, Papers, Psychology, Publications / 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, Papers, Psychology, Publications / 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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Response of cluster headache to psilocybin and LSD

June 27, 2006 / Headache Pain and Neurological Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / By / , ,

Abstract

The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

Sewell, R. A., Halpern, J. H., & Pope, Jr., H. G. (2006). Response of cluster headache to psilocybin and LSD. Neurology, 66(12), 1920–1922. http://dx.doi.org/10.1212/01.wnl.0000219761.05466.43
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Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

October 1, 2005 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 Ag/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

Carter, O. L., Burr, D. C., Pettigrew, J. D., Wallis, G. M., Hasler, F., & Vollenweider, F. X. (2005). Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. Journal of Cognitive neuroscience, 17(10), 1497-1508. http://dx.doi.org/10.1162/089892905774597191
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