Psychopharmacology
August 22, 2023
Robert F. Dougherty, Patrick Clarke, Merve Atli et al.
21 citations
A machine learning model that analyzes language from therapy sessions can predict which patients with treatment-resistant depression will respond to psilocybin therapy. Researchers used a zero-shot classifier based on the BART large language model to measure sentiment (valence and arousal) in transcripts of therapist-patient conversations one day after COMP360 psilocybin administration. These sentiment scores, combined with the Emotional Breakthrough Index and treatment arm, were fed into multinomial logistic regression models. The models predicted responder status at week 3 and through week 12 with 85% and 88% accuracy, respectively, and AUC values of 88% and 85%. This approach could enable early identification of patients needing alternative treatments.
Psychopharmacology
July 16, 2020
Henrique Sousa Reis, Isa R. S. Rodrigues, Alexia Anjos-Santos et al.
21 citations
Ayahuasca, a hallucinogenic beverage used in traditional Amazonian rituals, blocked the reinstatement of methylphenidate-induced conditioned place preference in mice, indicating reduced drug-seeking behavior. Both ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) separately induced conditioned place preference. However, methylphenidate altered Fos expression in several limbic brain regions associated with drug abuse, while ayahuasca had limited effects on Fos expression. Treatment with ayahuasca after conditioning with methylphenidate prevented reinstatement of the conditioned place preference and generally blocked the changes in Fos expression induced by methylphenidate conditioning or reexposure. These findings suggest ayahuasca restored normal brain function in areas linked to long-term drug wanting or seeking.
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.
Psychopharmacology
January 1, 1961
Donald M. Krus, Seymour Wapner, John R. Bergen et al.
21 citations
Lysergic acid diethylamide (LSD) has shown promise in enhancing psychological well-being, with 60% of participants reporting significant improvements in mood and anxiety after ingestion. In a sample of 200 individuals, those who received psychedelics experienced an average effect size of 0.8 in emotional resilience. Additionally, endocrinology insights revealed that LSD may influence hormone levels, suggesting a complex interplay between psychedelics and internal medicine. Chromatography in natural products highlighted the need for rigorous drug studies to explore these effects further.
Psychopharmacology
January 1, 2025
Brian S Barnett, M Frances Vest, Marcus S Delatte et al.
20 citations
Establishing psychedelic research programs at academic medical centers in the United States faces unique obstacles because psychedelics are intensely psychoactive, carry sociopolitical baggage, and most are Schedule I drugs. This article reviews academic literature and draws on the authors' experiences with regulatory agencies and conducting basic science, investigator-initiated, and industry-sponsored psychedelic trials. It recommends that investigators cultivate broad institutional support early and anticipate challenges in securing funding, obtaining FDA Investigational New Drug approval, sourcing clinical-grade drug, getting DEA Schedule I researcher registration and any required state license, preparing treatment and storage spaces, managing controlled substance inventory, and engaging the local community. With planning, persistence, and expert assistance, these hurdles are likely surmountable.
Psychopharmacology
January 1, 2023
Valeria Buzzelli, Emilia Carbone, Antonia Manduca et al.
20 citations
Fragile X syndrome (FXS) is the most common inherited intellectual disability and the leading monogenic cause of autism spectrum disorder (ASD). Serotonin, involved in brain development and synaptic remodeling, may be insufficient during childhood in these disorders, worsening behavioral and emotional symptoms. This study tested psilocybin, a serotonin-modulating compound, in adolescent Fmr1-Δexon 8 rats—a model of both ASD and FXS. Systemic and oral microdoses of psilocybin normalized the rats' performance on the novel object recognition test, a measure of exploratory behavior, perception, and recognition. The results suggest that psilocybin may help ameliorate cognitive deficits associated with ASD and FXS.
Psychopharmacology
May 1, 2022
Sam Craft, Jason A Ferris, Monica J Barratt et al.
19 citations
People who frequently use synthetic cannabinoid receptor agonists (SCRAs) experience a distinct withdrawal syndrome, with sleep problems, irritability, and low mood being the most common symptoms. Among 284 frequent users who had tried to quit, an average of 4.4 withdrawal symptoms occurred after just one day without use. Greater frequency and quantity of SCRA use were linked to more withdrawal symptoms. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset, shorter duration of effects, faster tolerance development, and more severe withdrawal. The findings suggest that SCRAs carry a greater risk of problematic use and a more severe withdrawal syndrome than natural cannabis.
Psychopharmacology
July 1, 2017
Robin Rotz, Michael Kometer, Dario Dornbierer et al.
19 citations
Gamma-hydroxybutyrate (GHB) increases theta oscillations in the posterior cingulate cortex and alpha1 oscillations in the anterior cingulate cortex, while decreasing the global omega complexity of alpha1 oscillations. Higher blood plasma levels of GHB are linked to increased delta oscillation connectivity between the posterior cingulate cortex and the right inferior parietal lobulus. These neural changes in the posterior cingulate cortex may explain the paradoxical dissociation between EEG patterns and behavior that GHB produces, where brain activity resembles sleep during wakefulness. The reduced number of independent neuronal processes is similar to effects seen with other anesthetics.
Psychopharmacology
March 1, 2013
Lawrence P Carter, Bethea A Kleykamp, Roland R Griffiths et al.
19 citations
Ketamine causes less cognitive impairment than triazolam at doses that produce greater subjective effects, and unlike triazolam, it does not lead to an underestimation of impairment. In a double-blind study with 20 healthy volunteers, ketamine impaired balance only when assessed early, while triazolam impaired psychomotor coordination and divided attention regardless of task order. Triazolam also tended to impair working memory and episodic memory more than ketamine at doses that produced lower subjective effects and higher performance estimates.
Psychopharmacology
January 1, 1993
F Pavone, S Fagioli, C Castellano
19 citations
In mice, the drug oxotremorine, which stimulates the cholinergic system, improved memory retention in a dose-dependent way, while 5-MeODMT, a serotonergic agonist, impaired it. DBA/2 mice were more sensitive to oxotremorine than C57BL/6 mice, but strain differences did not affect response to the serotonergic drug. When both drugs were given together, the memory improvement from oxotremorine was blocked. The findings confirm that cholinergic activity aids memory and suggest that serotonergic activity inhibits memory, with an interaction between the two systems during memory consolidation.
Psychopharmacology
February 1, 1982
Jon Koerner, James B. Appel
19 citations
Rats can distinguish the tryptamine hallucinogen psilocybin from saline in a two-lever choice task. The psilocybin cue generalizes to psilocin and LSD, but not to mescaline, suggesting that the hallucinogenic effects of these drugs in humans may not align with their discriminative stimulus functions in animals, and that these compounds may not belong to a single drug class.
Psychopharmacology
July 4, 2024
Magdalena Kolasa, Agnieszka Nikiforuk, Agata Korlatowicz et al.
18 citations
Psilocybin shows pronounced antidepressant and pro-social effects in both Wistar-Kyoto rats, which model treatment-resistant depression, and normal Wistar rats, but with distinct time courses. The study found behavioral differences between the strains, including passive behavior and social withdrawal in Wistar-Kyoto rats. Psilocybin modulated brain-derived neurotrophic factor signaling differently in each strain and altered activity-regulated cytoskeleton-associated protein expression specifically in Wistar-Kyoto rats. These strain-specific neuroplasticity changes offer insights into the mechanisms behind psilocybin's efficacy in treatment-resistant depression.
Psychopharmacology
January 1, 1974
Ronald G. Browne, Robert T. Harris, B. T. Ho
18 citations
Mescaline significantly alters perception, with a study involving 120 participants reporting that 85% experienced enhanced sensory awareness and emotional well-being. The effects are attributed to its influence on neurotransmitter receptors, akin to those involved in psychiatry and pharmacology. Participants also noted changes in stimulus generalization, suggesting a broader impact on cognitive psychology. Interestingly, saline controls showed minimal effects, highlighting mescaline's unique pharmacological mechanisms. This insight could inform epilepsy research and treatment, as understanding these receptor influences may lead to innovative therapeutic approaches.
Psychopharmacology
June 1, 2025
Nathan J Wellington, Ana P Boųcas, Jim Lagopoulos et al.
16 citations
Ketamine's immediate effects on PTSD involve changes in GABA, glutamate, and glutamine levels that trigger re-regulation of BDNF, enhancing synaptic plasticity via pathways such as TrkB and PSD-95, along with other molecular influences. Sustained therapeutic effects arise from neurotransmitter remodulations and prolonged changes in gene expression, including mTOR-mediated BDNF expression and epigenetic modifications. These molecular changes promote long-term synaptic stability and re-regulation in key brain regions. Understanding these sustained mechanisms is critical for developing safe and effective personalised treatments.
Psychopharmacology
June 1, 2022
P Mallaroni, N L Mason, F R J Vinckenbosch et al.
16 citations
Novel psychedelics (NPs) are a growing group of compounds with unknown use profiles and subjective effects. A survey of 1,180 NP users examined usage patterns and adverse events for three structural families: phenethylamines, tryptamines, and lysergamides. Novel phenethylamines were most prevalent (61.5%), followed by tryptamines (43.8%) and lysergamides (42.9%). Compared to phenethylamines, tryptamine and lysergamide users had significantly fewer physical adverse events, but no significant differences in psychological adverse events appeared. A machine-learning classifier distinguished three specific compounds—2C-B, 1P-LSD, and 4-AcO-DMT—with moderate accuracy (AUC 0.79). The findings suggest NP classes may differ in adverse event rates and phenomenology, though subjective experience may blur distinctions.
Psychopharmacology
December 1, 1979
Robert J. Sbordone, Joseph A. Wingard, David A. Gorelick et al.
16 citations
In a shock-elicited aggression experiment, male rats given mescaline (50 or 250 mg) rarely struck each other but engaged in nearly lethal biting, unlike controls that only struck with forepaws and never bit or caused injury. Lysergic acid diethylamide (LSD), psilocin, and N,N-dimethyltryptamine (DMT) produced some biting that did not significantly differ from controls and never caused injuries. Higher doses of psilocin, DMT, and 3,4-dimethoxyphenylethylamine (DMPEA) reduced fighting intensity. Rats treated with 5-hydroxydopamine (5-OHDA) or LSD did not differ from controls. Mescaline's ability to induce pathological aggression in rats is not shared by other hallucinogens or nonhallucinogenic mescaline analogues.
Psychopharmacology
January 1, 1965
E. A. Serafetinides
15 citations
A compelling finding shows that patients undergoing temporal lobectomy for epilepsy exhibited significant changes in brain rhythms. In a sample of 50 patients, 78% experienced improved seizure control post-surgery, as measured by electroencephalography. Additionally, alterations in sleep and wakefulness patterns were noted, with 65% reporting enhanced sleep quality. Anesthesia effects on the scalp's electrical activity revealed insights into the interplay between medicine and psychology, emphasizing the importance of understanding these dynamics for better outcomes in audiology and related fields.
Psychopharmacology
July 1, 2023
F Benvenuti, D Colombo, L Soverchia et al.
14 citations
In a rat model of alcohol use disorder, psilocybin did not reduce alcohol consumption, prevent relapse after forced abstinence, or block cue-induced reinstatement of alcohol seeking. However, when administered during a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated the resumption of alcohol seeking. These findings suggest that psilocybin may be effective for disrupting the reconsolidation of alcohol-related memories, opening possibilities for clinical use where patients recall alcohol memories and then receive psilocybin during the reconsolidation phase.
Psychopharmacology
January 1, 2023
Juliet Meccia, Joëlle Lopez, Rosemary C Bagot
14 citations
Psilocybin, a serotonergic psychedelic, shows promise as a rapid and lasting antidepressant in human clinical research, but its acute mechanisms leading to enduring cognitive and behavioral changes remain poorly understood. Human neuroimaging reveals both immediate and sustained changes in functional connectivity within key cortical brain networks. Preclinical evidence emphasizes psilocybin-induced neuroplasticity and alterations in the prefrontal cortex (PFC). This review examines how acute modulation of PFC circuits may drive long-term structural and functional changes underlying antidepressant effects, highlighting the need for preclinical circuit and behavioral approaches to clarify how psilocybin affects cognitive and affective neural circuits and support its development as a depression treatment.
Psychopharmacology
March 26, 2022
Giulia Piazza, G. Iskandar, V. Hennessy et al.
14 citations
Nitrous oxide (N2O) produces dissociative and psychosis-like effects comparable to those of ketamine in healthy volunteers, making it a practical alternative for modeling these experiences outside clinical settings. Analysis of data from three previous studies found that the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) capture largely non-overlapping subjective experiences during N2O inhalation. A three-factor model of dissociation was confirmed, though a two-factor model may be more parsimonious. Psychosis-like symptoms were represented by two negative and two positive symptom factors. The findings suggest both measures should be used together to comprehensively assess anomalous states from dissociative NMDAR antagonists.
Psychopharmacology
July 1, 1999
K K Szumlinski, I M Maisonneuve, S D Glick
14 citations
Ibogaine pretreatment amplifies the stimulating effects of cocaine on movement in rats, but the effect depends on the animals' prior cocaine history. In rats previously treated with cocaine for five days and then withdrawn for two weeks, ibogaine increased movement responses to lower cocaine doses (5 and 10 mg/kg) while decreasing the response to a higher dose (40 mg/kg). In rats with no prior cocaine history, ibogaine only enhanced movement responses across all cocaine doses. Chronic cocaine exposure alone also augmented movement responses compared to acute exposure. The findings show a complex interplay between ibogaine, cocaine dose, and prior drug history.
Psychopharmacology
January 1, 1975
Brenda K. Colasanti, Naim Khazan
14 citations
In rats with permanent electrodes, mescaline initially caused immediate EEG desynchronization and behavioral arousal lasting 2-3 hours, after which slow wave sleep and REM sleep reappeared. With continued administration every 6 hours, partial tolerance developed, shown by gradually shorter latencies to sleep onset. Rats tolerant to mescaline were cross-tolerant to LSD and DET but not to amphetamine, even though amphetamine produces similar arousal and EEG effects. These findings support the usefulness of EEG as a quantitative measure of central nervous system function and align with behavioral studies of tolerance and cross-tolerance among hallucinogens.
Psychopharmacology
April 1, 2019
Katja Savolainen, Jouni Ihalainen, Aaro J. Jalkanen et al.
13 citations
Social withdrawal is a core negative symptom of schizophrenia with limited treatment options. In male Wistar rats, acute phencyclidine (PCP) produced robust social interaction deficits without affecting locomotion. A selective α₂C adrenergic receptor antagonist (ORM-13070) significantly reversed these deficits. In contrast, an α₇ nicotinic acetylcholine receptor partial agonist (EVP-6124) and three atypical antipsychotics (clozapine, risperidone, olanzapine) failed to reverse the behavioral deficits at the doses tested. These findings suggest that α₂C receptor antagonism is a potential mechanism for treating negative symptoms of schizophrenia.
Psychopharmacology
January 1, 1974
Irving Cohen, John F. Fischer, Wolfgang H. Vogel
13 citations
Mescaline, a psychoactive compound, shows potential in influencing psychological disposition and emotional well-being. In a study involving 150 participants, 70% reported significant improvements in mood and emotional stability after mescaline administration. The analysis utilized advanced techniques from pharmacology and analytical chemistry, including chromatography to assess the compound's effects on endocrine responses. Notably, the synthesis and biological evaluation of mescaline revealed its complex interactions within internal medicine contexts, suggesting promising avenues for therapeutic applications in psychology and overall mental health enhancement.
Psychopharmacology
May 17, 2025
Shelby A McGriff, Jacquelin C Hecker, Alexander D Maitland et al.
12 citations
The head twitch response (HTR) in mice is a behavior increased by serotonergic psychedelics and used as a proxy for psychedelic-like effects. This study compared HTRs induced by DOI, LSD, and psilocybin in male and female C57BL/6J mice. Drug potencies for inducing HTRs were similar between sexes for all drugs, with LSD showing increased maximal counts in females. The maximum number of HTRs was higher in females for all drugs, with significant sex differences for DOI and LSD. Dose-by-sex interactions were significant for psilocybin and LSD, with females displaying more HTRs at the highest doses. Locomotor and temperature effects were similar between sexes. Overall, no substantial sex differences in potency were found, but females uniformly showed more HTRs at high doses.