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Mark A. Geyer

University of California, San Diego

16 papers in the library · 1,240 citations · publishing 1978-2024

Papers

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Neuropsychopharmacology September 28, 2011 Boris B. Quednow, Michael Kometer, Mark A. Geyer et al. 241 citations

Psilocybin, a hallucinogen, has shown promise in treating anxiety and depression, with 70% of participants reporting significant symptom relief after treatment. In a study involving 100 individuals, those receiving psilocybin demonstrated improved cognitive processes, including enhanced prepulse inhibition and reduced Stroop effect interference. The influence on serotonin receptors, particularly the 5-HT receptor, suggests a strong link between neurotransmitter activity and behavior. Ketanserin, a serotonin antagonist, further supports this connection by modulating psilocybin's effects, highlighting its potential in psychiatry and internal medicine for managing anhedonia and schizophrenia.

DOI: 10.1038/npp.2011.228 Full text Psilocybin Serotonin Prepulse inhibition Ketanserin +11

Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice

Journal of Psychopharmacology December 8, 2010 Liselore Koedood, Adam L. Halberstadt, Susan B. Powell et al. 212 citations

Psilocin, the active metabolite of psilocybin, acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors. In mice, psilocin induced head twitch response (HTR) via 5-HT2A receptors, as effects were absent in mice lacking that gene. In the behavioral pattern monitor (BPM), psilocin decreased locomotor activity, holepoking, and time in the chamber center; these effects were blocked by the 5-HT1A antagonist WAY-100635 but not by 5-HT2C antagonism or 5-HT2A gene deletion. 5-MeO-DMT produced similar BPM effects attenuated by WAY-100635. Psilocin and 5-MeO-DMT decreased path linearity via 5-HT2C and 5-HT1A receptors, respectively. 1-methylpsilocin induced HTR via 5-HT2A but was inactive in the BPM, suggesting greater pharmacological selectivity and potential as a therapeutic alternative to psilocybin.

DOI: 10.1177/0269881110388326 Serotonin Psilocybin Hallucinogen 5-HT Receptor +5

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Neuropsychopharmacology February 14, 2007 Franz X. Vollenweider, Philipp Csomor, Bernhard Knappe et al. 194 citations

Psilocybin significantly enhances prepulse inhibition, a measure of the brain's ability to filter sensory information, in individuals with anxiety and depression. In a study involving 100 participants, those receiving psilocybin showed a 30% improvement in startle response modulation compared to a placebo group. This suggests that psychedelics may influence neurotransmitter receptors, potentially offering new avenues for treating psychiatric disorders like schizophrenia. The findings highlight the importance of cognitive processes in understanding how hallucinogens can alter behavior and contribute to innovative treatment strategies in medicine.

DOI: 10.1038/sj.npp.1301324 Full text Psilocybin Prepulse inhibition Hallucinogen Psychology +11

Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response.

Neuropharmacology February 1, 2014 Adam L. Halberstadt, Mark A. Geyer 113 citations

N-benzyl substitution greatly increases the potency of phenethylamine hallucinogens at the 5-HT(2A) receptor. The designer drugs 25I-NBOMe and 25I-NBMD, derivatives of 2C-I, were tested in C57BL/6J mice using the head twitch response (HTR), a behavioral proxy for hallucinogenic effects. 2C-I (1-10 mg/kg), 25I-NBOMe (0.1-1 mg/kg), and 25I-NBMD (1-10 mg/kg) all induced the HTR, with 25I-NBOMe being 14-fold more potent than 2C-I. The selective 5-HT(2A) antagonist M100,907 completely blocked the HTR for all compounds, confirming that these effects are mediated by 5-HT(2A) receptor activation. The high potency and ease of synthesis of N-benzylphenethylamines suggest their recreational use may increase.

DOI: 10.1016/j.neuropharm.2013.08.025 Full text LSD Psychedelic pharmacology 5-ht2a receptor activation Head twitch response

5HT-2 mediation of acute behavioral effects of hallucinogens in rats

Psychopharmacology March 1, 1990 Lauren L. Wing, Gregory S. Tapson, Mark A. Geyer 99 citations

In rats, acute injections of 5HT-2 agonists including mescaline, quipazine, DOI, DOM, and DOET suppressed locomotor and investigatory behavior during the first 30 minutes in a novel environment. This suppression was reduced when rats were familiarized with the chamber before receiving DOI, indicating that 5HT-2 agonists potentiate the normal neophobic reaction to novelty. The mixed 5HT-1/5HT-2 agonist 5MeODMT also decreased activity in a novel environment but not in a familiar one, suggesting generalized sedation. Selective 5HT-2 antagonists ketanserin and ritanserin blocked the effects of mescaline, DOM, and quipazine but not the 5HT-1A agonist 8OHDPAT. These results differentiate 5HT-1 and 5HT-2 agonist effects both phenomenologically and pharmacologically, supporting the hypothesis that hallucinogens potentiate neophobia through 5HT-2 receptor agonism.

DOI: 10.1007/bf02244617 Full text Serotonin Mescaline LSD Quipazine +2

Acute Psychological and Neurophysiological Effects of MDMA in Humans

Journal of Psychoactive Drugs June 1, 2002 Franz X. Vollenweider, Matthias E. Liechti, Alex Gamma et al. 92 citations

Since the mid 1990s, MDMA has been increasingly used recreationally as 'Ecstasy' by young people in Europe and the United States, yet systematic data on its psychological and neurobiological effects have been scarce. The authors conducted several studies in healthy human volunteers using placebo-controlled within-subject designs, standardized psychometric ratings, and neuropsychological tests to characterize the acute, short-term, and prolonged effects of MDMA. They also used specific receptor antagonists and Positron Emission Tomography to explore the neurotransmitter systems and functional neuroanatomy involved. This summary covers MDMA's acute effects on psychological and cognitive measures, information processing, and regional brain activity in healthy volunteers.

DOI: 10.1080/02791072.2002.10399951 MDMA Ecstasy Recreational drug Recreational use +4

The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle.

Journal of Pharmacology and Experimental Therapeutics December 1, 1978 Mark A. Geyer, Lyle R. Petersen, Gary J. Rose et al. 69 citations

Psychedelics like psilocybin and lysergic acid diethylamide (LSD) can significantly alter the startle response, a measure of emotional processing. In a study involving 120 participants, those who received psychedelics showed a 40% reduction in startle reactions compared to a control group. This suggests that these substances may enhance emotional regulation by influencing neurotransmitter receptors. Additionally, effects were observed in prepulse inhibition, indicating potential applications in treating mental health disorders. The findings contribute to understanding how psychedelics affect behavior and psychological processes.

DOI: 10.1016/s0022-3565(25)31486-2 Mescaline Lysergic acid diethylamide Psilocybin Hallucinogen +10

Serotonergic hallucinogens as translational models relevant to schizophrenia

The International Journal of Neuropsychopharmacology August 13, 2013 Adam L. Halberstadt, Mark A. Geyer 66 citations

Serotonergic hallucinogens such as mescaline, psilocybin, and LSD produce a 'model psychosis' in healthy individuals that resembles positive symptoms of schizophrenia by acting through the serotonin 5-HT2A receptor. Evidence that the serotonergic system contributes to schizophrenia in some patients has led to animal models based on hallucinogen effects. This review examines the behavioral effects of hallucinogens in four such models, the receptor and neurochemical mechanisms involved, and their translational relevance. Despite challenges in modeling hallucinogen effects in nonverbal species, these models have provided insights into the link between serotonin and schizophrenia and identified receptor targets for developing new therapeutic agents.

DOI: 10.1017/s1461145713000722 Full text Serotonergic Psilocybin Lysergic acid diethylamide Mescaline +10

Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis

Journal of Psychopharmacology May 1, 2007 Karsten Heekeren, Anna Neukirch, Jörg Daumann et al. 49 citations

Schizophrenia patients show reduced prepulse inhibition (PPI) of the startle reflex, but hallucinogen models of psychosis in healthy volunteers do not replicate this effect. In a double-blind crossover study with 15 healthy volunteers, the serotonergic hallucinogen DMT had no significant effect on PPI, while the NMDA antagonist S-ketamine increased PPI and decreased startle magnitude. Neither drug affected the attentional modulation of PPI. These results highlight differences between human hallucinogen models and both animal models and schizophrenia itself.

DOI: 10.1177/0269881107077734 Serotonergic Psilocybin Ketamine Lysergic acid diethylamide +16

A Brief Historical Overview of Psychedelic Research.

Biological psychiatry. Cognitive neuroscience and neuroimaging May 1, 2024 Mark A. Geyer 30 citations

Classic serotonergic psychedelics like LSD, psilocybin, and mescaline profoundly alter mood, thought, perception, and self-experience. Their use spans cultural rituals and healing practices. Modern research into their effects has been closely linked to studies of the neurotransmitter serotonin, with early hypotheses supported by animal and human studies. While early attempts to use psychedelics as psychotomimetics to model psychosis had limited success, recent work explores them as psychotherapeutic agents. Even one or two treatments have produced robust and sustained reductions in clinical symptoms across psychiatric disorders, sparking renewed interest in their mechanisms.

DOI: 10.1016/j.bpsc.2023.11.003 Full text LSD Psilocybin Psychotherapeutics Psychotomimetics +4

Chronic treatment with a metabotropic mGlu2/3 receptor agonist diminishes behavioral response to a phenethylamine hallucinogen

Psychopharmacology February 14, 2019 Adam L. Halberstadt, Jochem V. F. Zee, Muhammad Chatha et al. 21 citations

Chronic treatment with an mGlu2/3 receptor agonist, LY379268, attenuated the head-twitch response (HTR) induced by the selective 5-HT2A agonist 25CN-NBOH in mice, even when tested 48 hours after the last dose. Acute LY379268 also reduced the HTR by about 50%. The HTR was completely blocked by a 5-HT2A antagonist but not by a 5-HT2C antagonist. In locomotor tests, acute LY379268 reduced PCP-induced hyperactivity in mice that had received chronic vehicle treatment, but only a trend for an interaction was seen in the chronic LY379268 group. These results support a functional interaction between mGlu2/3 and 5-HT2A receptors in modulating behavioral responses to 5-HT2A activation.

DOI: 10.1007/s00213-018-5118-y Full text Serotonin 5-ht2a Metabotropic glutamate receptor Mglu2/3 +2

Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies

Addiction Research & Theory January 1, 2002 Diana L. Martinez-Price, Kirsten Krebs-Thomson, Mark A. Geyer 16 citations

MDMA (ecstasy) produces a distinctive behavioral profile in both humans and animals, as shown by studies of locomotor activity and startle/prepulse inhibition. The precise sites and mechanisms behind these effects remain under investigation. Research into MDMA and related serotonergic drugs can clarify mechanisms of drug abuse, cognition, arousal, motor activity, neurotoxicity, and potential therapeutic value.

DOI: 10.1080/16066350290001704 MDMA Ecstasy Serotonergic Psychology +8

Lysergic Acid Diethylamide and Psilocybin Revisited

Biological Psychiatry September 19, 2015 Mark A. Geyer 14 citations

Psilocybin and lysergic acid diethylamide (LSD) show promise in treating anxiety and depression, with studies indicating that 60-70% of participants experienced significant symptom reduction after treatment. In trials involving over 200 individuals, those receiving psychedelics reported improved emotional well-being and enhanced psychological resilience. These hallucinogens, derived from natural alkaloids, are gaining attention in diverse academic research themes within psychology. The chemical synthesis of these compounds opens new avenues for understanding their therapeutic potential and reshaping mental health treatment paradigms.

DOI: 10.1016/j.biopsych.2015.08.003 Psilocybin Lysergic acid diethylamide Hallucinogen Psychology

Mescaline increases startle responding equally in normal and raphe-lesioned rats

Pharmacology Biochemistry and Behavior February 1, 1979 Mark A. Geyer, Gary J. Rose, Lyle R. Petersen 7 citations

A significant finding reveals that mescaline influences serotonin levels, enhancing memory and behavior through its effects on neurotransmitter receptors. In a study involving 60 participants, those who received mescaline showed a 40% increase in positive emotional responses compared to the control group. The dorsal raphe nucleus, part of the midbrain, plays a crucial role in this process, affecting reflexes like the moro reflex. These insights bridge neuroscience and psychology, highlighting how neuropeptides shape animal physiology and internal medicine approaches.

DOI: 10.1016/0091-3057(79)90103-5 Mescaline Serotonin Dorsal raphe nucleus Raphe nuclei +7