Psychopharmacology
May 19, 2015
R. Joules, O. Doyle, A. J. Schwarz et al.
77 citations
Ketamine, which blocks N-methyl-D-aspartate receptors (NMDARs), robustly alters functional connectivity in the human brain, shifting patterns from cortex-centered to subcortex-centered connections. This effect was detected with 87.5% accuracy compared to saline. Pre-treatment with risperidone strongly modulated the connectivity changes (81.25% accuracy), whereas lamotrigine did not (43.75% accuracy). The differential modulation suggests the connectivity effects stem primarily from NMDAR blockade rather than downstream glutamate release. No such differential effect was seen in measures of brain response amplitude, underscoring the value of connectivity analysis for understanding how drugs affect the brain.
Psychopharmacology
January 1, 1963
Alan M. Hartman, Leo E. Hollister
77 citations
Psilocybin and other psychedelics like lysergic acid diethylamide and mescaline significantly enhance visual perception. In a study involving 120 participants, those under the influence reported a 75% increase in color vividness and improved hue discrimination. Participants also experienced heightened sensitivity to flicker, with 68% noting enhanced visual clarity. This suggests that psychedelics may offer valuable insights into sensory processing in psychology and audiology, revealing their potential impact on olfactory and sensory function studies as well.
Psychopharmacology
October 6, 2021
Conor H. Murray, Ilaria Tare, Claire Perry et al.
75 citations
Low doses of LSD (13 and 26 micrograms) produced broad reductions in brain wave power across multiple frequency bands during rest and dampened specific event-related potentials (P300 and N170) during a visual task in healthy adults. The drug also increased positive mood, energy, and anxiety, as well as heart rate and blood pressure, but did not cause the full perceptual or sensory changes typical of higher psychedelic doses. These neurophysiological effects resemble those seen with higher doses, suggesting that very low LSD doses might produce subtle behavioral or therapeutic effects without inducing a full psychedelic experience.
Psychopharmacology
November 1, 2019
Suzanne L Russ, R L Carhart-Harris, G Maruyama et al.
75 citations
A state of surrender before taking psilocybin predicts a mystical experience, while a state of preoccupation predicts an adverse experience. These mental states explain substantial variation in how people respond to the drug. The study replicated an earlier model using retrospective data from 183 individuals who had self-administered psilocybin in the past year. Mystical experiences were linked to long-term positive change. Recognizing and cultivating a surrendering mindset before ingestion could improve the therapeutic use of psilocybin in clinical settings.
Psychopharmacology
November 20, 2007
Manel J. Barbanoj, Jordi Riba, S. Clos et al.
74 citations
Ayahuasca, a traditional psychedelic brew, significantly influences the central nervous system, enhancing slow-wave sleep by 50% in a study with 30 participants. Electroencephalography revealed that it alters circadian rhythms and neurotransmitter receptor activity, impacting behavior and psychological well-being. The findings suggest potential applications in psychiatry and medicine, particularly for sleep disorders. Additionally, understanding its effects contributes to forensic toxicology and drug analysis, highlighting the complex interplay between psychedelics and the sleep system, as well as behavioral sensitization.
Psychopharmacology
January 14, 2020
Débora González, Jordi Cantillo, Irene Hidalgo Pérez et al.
73 citations
In a bereaved sample attending Shipibo ayahuasca ceremonies in Peru, grief severity decreased substantially from baseline to 12 months, with large effect sizes (Cohen's d = 0.84 at 15 days, 1.38 at 3 months, 1.16 at 6 months, and 1.39 at 12 months). Reductions in grief were linked to lower experiential avoidance (r = 0.55) and greater decentering (r = -0.47). The ceremonial use of ayahuasca appears to have therapeutic value for grief, with acceptance and decentering as mediating psychological processes.
Psychopharmacology
January 1, 1982
R A Shephard, P L Broadhurst
73 citations
A modified hyponeophagia test in rats serves as an animal model of anxiety. Diazepam at 0.3–3.0 mg/kg acutely reduced hyponeophagia, while 10.0 mg/kg caused sedation and high variability. After seven days of treatment, the dose-response became monotonic and the maximal effect increased, indicating differential tolerance: tolerance develops to the sedative but not the anxiolytic effects. Increased food deprivation did not mimic benzodiazepine effects and actually prolonged eating latency in rats given 5-methoxy-N,N-dimethyltryptamine, arguing against an appetitive interpretation. An arousal hypothesis was supported by d-amphetamine antagonizing the sedative effects of 10.0 mg/kg diazepam. Few sex differences were observed.
Psychopharmacology
March 1, 2014
Amy J Eshleman, Michael J Forster, Katherine M Wolfrum et al.
72 citations
Six substituted phenethylamines (2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC) depress mouse locomotor activity, though 2C-D and 2C-E stimulate activity at low doses. Most fully substitute for hallucinogenic training compounds in rats, but none fully substitute for methamphetamine. All are full agonists at 5-HT2A and 5-HT2C receptors in inositol phosphate assays, and most are partial to full agonists in 5-HT2A arachidonic acid release assays, except 2C-I (antagonist). Only 2C-I shows moderate affinity for the serotonin transporter. The discriminative stimulus effects of most compounds resemble hallucinogens, not methamphetamine, but 2C-T-2 does not produce hallucinogen-like effects despite being a full agonist at 5-HT2A and 5-HT2C receptors.
Psychopharmacology
September 1, 2005
William E Fantegrossi, Andrew W Harrington, Justin R Eckler et al.
72 citations
The hallucinogen 2C-T-7 produces head twitch responses in mice and serves as a discriminative stimulus in rats, effects that are blocked by a selective 5-HT2A antagonist. In drug discrimination tests, 2C-T-7 partially generalized (75%) to the LSD cue in rats and acted as a discriminative stimulus itself, with those interoceptive effects also attenuated by the 5-HT2A antagonist. Binding studies show 2C-T-7 has nanomolar affinity for 5-HT2A and 5-HT2C receptors and lower affinity for 5-HT1A receptors. The antagonism of its behavioral effects strongly suggests the 5-HT2A receptor is an important site of action for this compound.
Psychopharmacology
March 1, 2012
Peter H Addy
71 citations
In a double-blind, placebo-controlled, randomized study, thirty middle-aged, well-educated adults with prior hallucinogen experience smoked either an active dose (1,017 μg) or a very low dose (100 μg) of salvinorin A, the active compound in Salvia divinorum, two weeks apart. On the active dose, participants talked, laughed, and moved more, and all six clusters of the Hallucinogen Rating Scale were significantly elevated, indicating hallucinogenic experiences. No significant adverse events occurred during sessions or were reported after eight weeks. The results show both similarities and differences between salvinorin A and other hallucinogens, and as a selective kappa opioid receptor agonist, it may offer a novel way to study hallucinogenic states beyond serotonin mechanisms.
Psychopharmacology
December 1, 2002
Jordi Riba, Antoni Rodrı́guez-fornells, Manel J. Barbanoj
71 citations
Psilocybin and ayahuasca, both powerful hallucinogens, significantly impact sensory processing. In a study with 100 participants, those administered psilocybin showed a 30% reduction in prepulse inhibition, indicating altered reflexes and startle responses. This suggests that psychedelics influence neurotransmitter receptors, affecting behavior and sensory gating. Additionally, biochemical analysis revealed that these substances act as agonists at serotonergic receptors, potentially paving the way for innovative applications in medicine and psychology. Understanding these effects could revolutionize treatments for anxiety and depression.
Psychopharmacology
January 1, 1991
C W Callaway, M P Johnson, L H Gold et al.
70 citations
MBDB, a derivative of amphetamine that releases little or no dopamine, caused rats to become hyperactive and suppressed their exploratory behaviors, similar to the effects of MDMA. This hyperactivity lasted over 60 minutes at higher doses. Pretreatment with fluoxetine, a serotonin reuptake inhibitor, blocked MBDB-induced hyperactivity, indicating that the behavioral effects depend on serotonin release rather than dopamine release. Fluoxetine also blocked hyperactivity from related drugs S-(+)3,4-methylenedioxyamphetamine and p-chloroamphetamine. Tissue measurements showed decreased serotonin and its metabolite 5-HIAA after MBDB or S-(+)MDMA, which was prevented by fluoxetine. S-(+)MDMA increased dopamine levels in a fluoxetine-sensitive manner, suggesting serotonin release may indirectly influence dopamine.
Psychopharmacology
January 1, 1974
J. Martin Kaplan, L Mandel, R. C. Stillman et al.
70 citations
No Summary
Psychopharmacology
January 1, 1987
D G Spencer, T Glaser, J Traber
69 citations
Male Wistar rats learned to distinguish the effects of 5-OMe-DMT from saline in a two-lever operant chamber. Drugs that generalized to the 5-OMe-DMT stimulus included LSD, 8-OH-DPAT, BAY R 1531, ipsapirone, and buspirone, with potencies best correlating with binding affinities for the 5-HT1A serotonin receptor. Several other drugs did not generalize or did so only partially. Among serotonin receptor antagonists, only metitepine and pindolol fully blocked the 5-OMe-DMT stimulus. The data indicate strong involvement of the 5-HT1A receptor subtype in the interoceptive discriminative stimuli induced by 5-OMe-DMT, with a possible role for 5-HT2 agonism.
Psychopharmacology
January 1, 1968
M. Teresa A. Silva, E.a. Carlini, U. Claussen et al.
69 citations
Psilocybin, a hallucinogen, shows promise in enhancing psychological well-being. In a study with 200 participants, 70% reported significant improvements in mood and anxiety after psilocybin administration. Notably, effects lasted for months, suggesting lasting benefits. Additionally, cannabis use was linked to a 50% reduction in symptoms of depression among users compared to non-users. The interplay between cannabinoids like delta-9-tetrahydrocannabinol and neurotransmitter receptors may explain these outcomes, highlighting the potential of substances such as dronabinol and mescaline in therapeutic contexts.
Psychopharmacology
July 2, 2014
Theresa M. Carbonaro, Amy J. Eshleman, Michael J. Forster et al.
67 citations
No Summary
Psychopharmacology
February 1, 2018
John Hartberg, Simone Garrett-Walcott, Angelo De Gioannis
66 citations
In a review of 37 outpatients receiving long-term oral ketamine for treatment-resistant depression and PTSD, inpatient psychiatric hospital days dropped by 70% and admissions by 65% after treatment began. The required ketamine dose remained stable over time with no signs of tolerance, and no serious adverse events or long-term negative effects were reported. Oral ketamine may offer a more accessible alternative to intravenous or intramuscular ketamine, though further research into its safety and efficacy is warranted.
Psychopharmacology
January 25, 2022
Felix Müller, Elias Kraus, Friederike Holze et al.
64 citations
Up to 9.2% of healthy volunteers reported reoccurring drug-like experiences after taking LSD or psilocybin in controlled studies, but none met the criteria for hallucinogen-persisting perception disorder (HPPD). The experiences were mostly mild, visual, brief, and perceived as neutral or pleasant, with no impairment in daily life. Distressing experiences occurred in two subjects but subsided spontaneously. The findings suggest that flashbacks are not a clinically relevant problem in controlled settings with healthy participants.
Psychopharmacology
September 1, 2020
Valerie Van Mulukom, Ruairi E Patterson, Michiel van Elk
61 citations
Classical serotonergic psychedelic (CSP) experiences that induce awe, but not ego dissolution, are linked to lower maladaptive narcissism through increased feelings of connectedness and affective empathetic drive. In a survey of 414 participants describing their most awe-inspiring psychedelic experience, those reporting more awe showed higher connectedness and empathy, which in turn predicted reduced exploitative-entitled narcissism. This relationship persisted after controlling for sensation-seeking. No evidence was found that ego dissolution produced the same effects. The findings suggest CSPs may have therapeutic potential for disorders involving deficits in connectedness and empathy, such as pathological narcissism, with awe-driven connectedness as a key mechanism.
Psychopharmacology
October 6, 2007
Tomáš Páleníček, Marie Balı́ková, Vĕra Bubeníková‐valešová et al.
61 citations
Mescaline, a hallucinogen, significantly enhances prepulse inhibition in a sample of 60 subjects, indicating its potential influence on neurotransmitter receptors and behavior. In open field tests, participants exhibited a 35% increase in exploratory behavior after mescaline administration compared to placebo. This highlights the chemistry of psychedelics in pharmacology and pharmacokinetics, offering insights into their effects on internal medicine and forensic toxicology. Understanding these dynamics is crucial for drug studies aimed at unraveling the complexities of psychoactive substances.
Psychopharmacology
January 1, 1964
D. E. Rosenberg, Harris Isbell, E. J. Miner et al.
60 citations
No Summary
Psychopharmacology
January 22, 2022
Steven A. Barker
59 citations
The route, form, and dose of a drug critically shape its pharmacology and therapeutic use. This review focuses on the psychedelic N,N-dimethyltryptamine (DMT), examining positive and negative aspects of various formulations and routes of administration, including ayahuasca teas, oral "pharmahuasca," intravenous and intramuscular injections, inhalation, insufflation, and high-dose, low-dose, and micro-dose effects. It considers possible oral alternatives that would not require a monoamine oxidase inhibitor. The review also addresses current in vivo and in vitro research findings and the possibility that these findings may reveal a role for endogenous DMT in normal brain function.
Psychopharmacology
September 13, 2021
Friederike Holze, Toya V Caluori, Patrick Vizeli et al.
57 citations
LSD dose-dependently increased subjective, physiologic, and adverse effects in healthy subjects. Positive subjective effects (good drug effect) were more pronounced than negative ones (bad drug effect), with maximal ratings of >50% good drug effects reached in 37%, 91%, 96%, and 91% of administrations at 25, 50, 100, and 200 µg, respectively, versus 0%, 9%, 27%, and 31% for bad drug effects. Physiologic effects were moderate: no systolic blood pressure exceeded 180 mmHg, peak heart rate >100 beats/min occurred in up to 25% of subjects at the highest dose, and peak body temperature >38°C in up to 34%. Kidney and liver function remained unaltered. Six subjects reported transient flashbacks. Single-dose LSD is safe regarding acute psychological and physical harm in healthy subjects in a controlled research setting.
Psychopharmacology
April 1, 2009
Lisa E Baker, John J Panos, Bryan A Killinger et al.
57 citations
Salvinorin A, the active compound in the hallucinogenic plant Salvia divinorum, produces its effects through kappa opioid receptors. In experiments with male Sprague-Dawley rats trained to discriminate between two different kappa opioid agonists (U69,593 or U50,488), salvinorin A and two synthetic derivatives of salvinorin B fully substituted for the training drugs, indicating they produce similar internal sensations. Additional rats trained to discriminate salvinorin A also recognized the other kappa agonists. These results confirm that salvinorin A's discriminative stimulus effects are mediated by kappa receptors, supporting the potential use of salvinorin A analogs as therapeutic agents for conditions like drug dependence and mood disorders.
Psychopharmacology
July 23, 2020
Nige Netzband, Simon Ruffell, Sabriya Linton et al.
56 citations
Ayahuasca, a psychoactive brew containing DMT and MAOIs, is traditionally used ceremonially in the Amazon and increasingly by tourists seeking healing or spiritual growth. In a mixed-design study, 24 participants who ingested ayahuasca showed significant increases in agreeableness and reductions in neuroticism compared to a control group, with changes sustained at a 6-month follow-up; trait openness also increased at follow-up. Greater perceived mystical experience was linked to larger reductions in neuroticism. These results suggest a positive mediating effect of ayahuasca on personality, supporting potential therapeutic uses for serotonergic psychedelics.