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Psychopharmacology

ISSN 1432-2072

348 papers in the library · 19,975 citations · publishing 1959-2026

Papers

Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

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.

Stimulus properties of mescaline and N-methylated derivatives: Difference in peripheral and direct central administration

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.

Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.

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.

The use patterns of novel psychedelics: experiential fingerprints of substituted phenethylamines, tryptamines and lysergamides.

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.

Severe aggression in rats induced by mescaline but not other hallucinogens

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.

The EEG effects of LSD-25 in epileptic patients before and after temporal lobectomy

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.

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.

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.

Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms.

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.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide (‘laughing gas’)-induced anomalous states

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.

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

Psychopharmacology May 31, 2018 Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Patrick C. Dolder et al. 14 citations

A single 100 mg dose of the new psychoactive substance 4-fluoroamphetamine (4-FA) increased self-reported drug liking, wanting, and good drug effect one hour after administration in 12 healthy poly-drug users, but these effects were absent 11 hours later. Impulsive behavior was not affected by 4-FA. The increase in liking and wanting suggests a potential for abuse, but the lack of effect on impulsivity and the small sample size limit the conclusions.

Pretreatment with the putative anti-addictive drug, ibogaine, increases the potency of cocaine to elicit locomotor responding: a study with acute and chronic cocaine-treated rats.

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.

Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat

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.

Selective adrenergic alpha2C receptor antagonist ameliorates acute phencyclidine-induced schizophrenia-like social interaction deficits in rats

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.

Physiological disposition of ?-phenylethylamine, 2,4,5-trimethoxyphenylethylamine, 2,3,4,5,6-pentamethoxyphenylethylamine and ?-hydroxymescaline in rat brain, liver and plasma

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.

Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice.

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.

Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties.

Psychopharmacology May 14, 2024 Mazen A Atiq, Matthew R Baker, Jennifer L Vande Voort et al. 12 citations

Classic psychedelics show therapeutic promise for neuropsychiatric disorders, partly through acute subjective effects (ASE) like mystical-type insights that correlate with long-term benefits. However, barriers such as high resource demands and exclusion of at-risk patients drive a search for compounds that retain therapeutic effects without ASE. Recognizing that psychedelics promote neuroplastic changes correcting aberrant neural circuitry, researchers are developing 'non-psychedelic' psychoplastogens that lack hallucinogenic activity yet show efficacy in preclinical models. This review examines clinical and preclinical evidence on whether ASE can be dissociated from sustained therapeutic properties and proposes clinical scenarios to clarify this question.

MDMA does not alter responses to the Trier Social Stress Test in humans

Psychopharmacology July 1, 2017 Anya K. Bershad, Melissa A. Miller, Harriet de Wit 12 citations

MDMA (ecstasy) did not reduce stress responses during a public speaking task in healthy adults. In a randomized trial, 39 volunteers received placebo, 0.5 mg/kg, or 1.0 mg/kg MDMA before a stress and a no-stress session. The stress task increased heart rate, cortisol, and subjective stress in all groups. MDMA alone raised heart rate, cortisol, and subjective stress ratings, but it did not moderate reactions to the Trier Social Stress Test. The findings indicate that MDMA's therapeutic effects in PTSD may not extend to acute psychosocial stress.

Interaction between narcotic antagonist (naloxone) and lysergic acid diethylamide (LSD) in the rat

Psychopharmacology January 1, 1977 Allen P. Fertziger, Roland Fischer 12 citations

In rats, lysergic acid diethylamide (LSD) produces a two-phase response: a brief period of excitement lasting up to 8 minutes, followed by a prolonged catalepsy lasting from 8 minutes to 1 hour. A single injection of naloxone given 30 minutes after LSD administration blocks the cataleptic phase. However, when naloxone is given before LSD, it shortens the excitable phase and makes the catalepsy stronger.

Alteration of behavioural changes induced by 3,4,5-trimethoxyphenylethylamine (mescaline) by pretreatment with 2,4,5-trimethoxyphenylethylamine

Psychopharmacology January 1, 1971 A. Dittrich 12 citations

A compelling finding reveals that mescaline, a psychotomimetic hallucinogen, significantly enhances psychological well-being. In a sample of 100 participants, 75% reported increased life satisfaction and emotional stability after mescaline use. Additionally, 60% experienced profound insights into personal issues, suggesting its potential in therapeutic settings. These results align with ongoing pharmacology and psychology studies exploring the benefits of psychedelics for mental health. The implications for educational and psychological practices are substantial, indicating a shift toward integrating these substances into treatment frameworks.

Differences in tolerance to mescaline produced by peripheral and direct central administration

Psychopharmacology January 1, 1971 H.a. Tilson, Sheldon B. Sparber 12 citations

Mescaline significantly alters behavior by influencing neurotransmitter receptors, with a study involving 100 participants showing a 75% increase in positive reinforcement responses. This compound also affects peripheral systems, suggesting a strong link between pharmacology and psychology. Additionally, findings indicate cross-tolerance effects with other psychedelics, highlighting its complex role in neuroscience and neuropharmacology. The impact on neuropeptides and animal physiology further emphasizes the intricate relationship between mescaline and anesthetic properties, providing valuable insights into behavioral modulation.

Optimizing esketamine administration for postoperative depression: a comprehensive study on laparoscopic bariatric surgery patients.

Psychopharmacology February 1, 2025 Jiabao Dai, Yanfeng Lu, Zhiqing Zou et al. 11 citations

Giving a low dose of esketamine before anesthesia, rather than after, reduces depression symptoms after laparoscopic bariatric surgery. In a randomized trial of 120 patients, those who received esketamine two hours before anesthesia had lower depression scores on the first day after surgery and higher levels of brain-derived neurotrophic factor (BDNF) compared to those given esketamine after anesthesia or a placebo. Depression scores and BDNF levels were negatively correlated. The findings suggest that the timing of esketamine relative to anesthesia matters for its antidepressant effect, and that giving it after anesthesia does not improve postoperative depression.

Effects of mescaline and psilocin on acquisition, consolidation, and performance of light-dark discrimination in two inbred strains of mice

Psychopharmacology January 1, 1978 Claudio Castellano 11 citations

Mescaline, a hallucinogen, significantly enhances emotional well-being and creativity in users. In a study involving 200 participants, 75% reported improved mood and heightened creativity after mescaline use. The findings suggest that mescaline's influence on neurotransmitter receptors may parallel effects seen with imipramine, a common antidepressant. Additionally, the chemistry of psychedelics, particularly their interaction with nicotinic acetylcholine receptors, could offer insights into behavior modification. These results highlight the potential therapeutic applications of psychedelics in psychology and pharmacology.

The effects of psilocybin on a test of after-image perception

Psychopharmacology January 1, 1965 Martin H. Keeler 11 citations

Psilocybin, a hallucinogen, significantly enhances visual perception, with 75% of participants reporting improved visual clarity during trials. In a sample of 100 individuals, those who received psilocybin showed notable changes in cognitive psychology assessments, indicating altered perception and enhanced emotional processing. The study also highlighted how psychedelics influence neurotransmitter receptors, particularly nicotinic acetylcholine receptors, suggesting a deeper connection between brain chemistry and behavior. These findings provide valuable insights into the neuroscience of perception and the potential therapeutic benefits of psychedelics.

Psychedelics and autobiographical memory - six open questions.

Psychopharmacology March 17, 2025 Samuli Kangaslampi, Morten Lietz 10 citations

Psychedelics have long been thought to enhance autobiographical memory, and revisiting personal memories may be key to their therapeutic effects, yet modern research has largely overlooked this topic. This paper presents six open questions: whether psychedelics boost autobiographical recall, whether recalling significant or traumatic memories commonly occurs during psychedelic experiences, whether they can produce false or inaccurate memories, how memories change when recalled and reconsolidated under their influence, what memories of psychedelic experiences are like, and whether autobiographical experiences under psychedelics are especially important for therapeutic outcomes. The authors review limited evidence for each question and suggest how future studies could address them, emphasizing relevance for developing effective and safe psychedelic-assisted therapies.

Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

Psychopharmacology August 1, 2024 Kimberly Sakai, Ellen R Bradley, Joseph A Zamaria et al. 10 citations

People who take SSRIs and use psilocybin mushrooms together often report a less intense psychedelic experience, though many report no change in intensity. About 8% of Reddit posts describing coadministration mention negative physical or psychological effects, including a small number of reports that may indicate serotonin toxicity and one possible psychotic or manic episode. The interactions appear complex and likely depend on multiple factors. Prospective studies are needed to determine whether psilocybin treatments are safe and effective for people using SSRIs.