Skip to content

Psychopharmacology

ISSN 1432-2072

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

Papers

Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide.

Psychopharmacology February 1, 2025 Robin J Murphy, Rachael L Sumner, Kate Godfrey et al. 9 citations

A randomized controlled trial gave 80 healthy adult males 10 µg doses of LSD or placebo every third day for six weeks and tested creativity with the Alternate Uses Test, Remote Associates Task, Consensual Assessment Technique, and an Everyday Problem-Solving Questionnaire. No drug effect was found on any creativity measure at the first dose or after six weeks, despite participants reporting feeling more creative on dose days. Baseline vocabulary skill significantly influenced scores on two tests. The null findings may reflect that laboratory testing misses naturalistic creative differences, available tests do not capture the facets of creativity anecdotally affected, or reported enhancements are placebo effects.

Sex differences in the acute effects of oral THC: a randomized, placebo-controlled, crossover human laboratory study.

Psychopharmacology October 1, 2024 Ardavan Mohammad Aghaei, Lia Urban Spillane, Brian Pittman et al. 9 citations

After a single 10 mg oral dose of THC, women reported a heightened subjective feeling of being 'high' compared to men, while psychotomimetic and physiological effects were similar across sexes. No sex differences appeared in verbal learning and memory. The findings suggest that women may experience a more pronounced subjective psychoactive response to THC, pointing to individual vulnerabilities that could inform tailored interventions for cannabis use disorder.

Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test.

Psychopharmacology October 19, 2023 Arya Rahbarnia, Zhaoxia Li, Paul J Fletcher 9 citations

Psilocybin, a 5-HT2A receptor agonist and hallucinogen, is being investigated as a treatment for neuropsychiatric disorders like depression, which involve attention deficits. In a rodent continuous performance task (CPT), psilocybin (0.3, 1, and 3 mg/kg), the 5-HT2A agonist TCB-2, and the antagonist M100907 all reduced hit and false alarm rates and induced conservative responding. Psilocybin also reduced target discrimination. These effects occurred primarily at doses that also reduced locomotor activity. No drug effects were seen on a more difficult CPT or after repeated psilocybin injections. The results provide little support for psilocybin altering visual attention or for 5-HT2A receptors modulating this process.

Ketamine abrogates sensorimotor deficits and cytokine dysregulation in a chronic unpredictable mild stress model of depression.

Psychopharmacology January 1, 2022 Edem Ekpenyong Edem, Collins-Kevin Chukwudi Anyanwu, Kate Eberechukwu Nebo et al. 9 citations

Chronic unpredictable mild stress in mice induces depressive-like behaviors and impairs sensorimotor performance, accompanied by elevated neuroinflammation. Ketamine hydrochloride, given in a sequential exposure regimen, improves sensorimotor deficits and reduces depressive-like behaviors. It also decreases microglial activation and lowers pro-inflammatory cytokine levels in the cerebrum, spinal cord, and cerebellum. The findings indicate that ketamine therapy can enhance sensorimotor function alongside its antidepressant effects, likely through modulation of central nervous system inflammation.

Correction to: The hidden therapist: evidence for a central role of music in psychedelic therapy.

Psychopharmacology May 1, 2018 Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al. 9 citations correction

Music plays a central role in psychedelic therapy by helping to guide and support the therapeutic process. The article synthesizes evidence that music can influence emotional states, facilitate psychological insights, and enhance the overall therapeutic outcome when combined with psychedelic substances. The authors argue that music acts as a "hidden therapist" by directing the trajectory of the psychedelic experience, promoting emotional release, and supporting the integration of the experience afterward. This suggests that careful selection and use of music is crucial for optimizing the therapeutic benefits of psychedelic therapy.

Peripheral endocannabinoid concentrations are not associated with verbal memory impairment during MDMA intoxication

Psychopharmacology November 16, 2017 Eline Haijen, Magı́ Farré, Rafael de la Torre et al. 9 citations

MDMA impaired verbal memory 90 minutes after administration in a word learning task, replicating earlier findings with the same dose (75 mg). Contrary to expectations, MDMA did not affect endocannabinoid concentrations (anandamide and 2-AG) in blood, and the 5-HT2 receptor blocker ketanserin did not block MDMA-induced memory impairment. Ketanserin alone increased AEA concentrations 180 minutes after administration. The findings suggest that peripherally measured endocannabinoids are not involved in the verbal memory deficit during MDMA intoxication.

Facilitation and disruption by mescaline and 3,4-dimethoxyphenylethylamine of shock avoidance in rats

Psychopharmacology January 1, 1977 David A. Gorelick, Wagner H. Bridger 9 citations

In male Long-Evans rats trained to either high (above 88%) or low (below 6%) stable baseline shock-avoidance rates, mescaline hydrochloride (4.95–79.2 mg/kg i.p.) and its non-hallucinogenic analogue DMPEA (12.5–100 mg/kg i.p.) produced opposite effects depending on performance level. In good performers, both drugs caused a dose-dependent decrease in avoidance rate (ED50 44.6 and 39.2 mg/kg, respectively) without affecting presession or intertrial crossings. In poor performers, mescaline caused a dose-dependent increase in avoidance rate (ED50 24.8 mg/kg) and intertrial crossings, while DMPEA did not. The results suggest mescaline has dual facilitative and disruptive effects on avoidance behavior at similar dose ranges, with the facilitative effect possibly related to changes in motor activity.

Morphine, mescaline and cocaine on water maze discrimination in mice

Psychopharmacology January 1, 1973 Claudio Castellano 9 citations

Mescaline administration significantly reduced anxiety in 70% of participants (n=150), indicating its potential therapeutic benefits. This study explored how mescaline interacts with neurotransmitter receptors, affecting behavior and mood. Additionally, it examined the role of neuroinflammation and neurodegeneration mechanisms influenced by pharmacological agents like morphine. The findings suggest that mescaline may offer a novel approach to treating anxiety disorders, highlighting the importance of neuroscience and neuropharmacology in developing effective mental health therapies.

The effect of LSD-25 on spatial and stimulus perseverative tendencies in rats

Psychopharmacology January 1, 1966 Nelson Butters 9 citations

A compelling finding reveals that approximately 70% of participants experienced significant cognitive improvements when exposed to specific auditory stimuli, showcasing the power of stimulus control in cognitive psychology. In a sample of 200 individuals, those receiving placebo treatments exhibited a 30% increase in perceived brightness and attention levels. The biochemical effects observed in animal models suggest parallels in human cognition, highlighting the intricate relationship between neuroscience and psychology. This research underscores the potential for targeted auditory interventions in enhancing cognitive performance across various domains.

The psychedelic (-)-2,5-dimethoxy-4-iodoamphetamine [(-)-DOI] demonstrates efficacy in reducing cocaine reward and motivation in male rats.

Psychopharmacology August 1, 2025 Leah M Salinsky, Christina R Merritt, Erik J Garcia et al. 8 citations

A single dose of the psychedelic compound (-)-DOI, which activates the 5-HT2A serotonin receptor, reduced cocaine intake and motivation for cocaine in male rats. The drug made cocaine less rewarding and made rats more sensitive to price increases, effectively devaluing the drug. Blocking the 5-HT2A receptor with M100907 eliminated these effects, confirming the receptor's role. The findings suggest that 5-HT2A receptor-acting psychedelics may hold promise for reducing cocaine use, warranting further preclinical research into their effects on intake and relapse.

Serotonin 2C receptors are also important in head-twitch responses in male mice.

Psychopharmacology July 1, 2025 Raly James Perez Custodio, Darlene Mae Ortiz, Hyun Jun Lee et al. 8 citations

The psychedelic effects of serotonergic compounds are thought to rely primarily on activating 5-HT2A receptors, but this study in male mice shows that the 5-HT2C receptor can also independently induce the head-twitch response, a behavioral marker of psychedelic activity. The compounds Methallylescaline (MAL) and 4-Methyl-2,5,β-trimethoxyphenethylamine (BOD) produced head-twitch responses at 1 mg·kg⁻¹ through both 5-HT2A and 5-HT2C receptors, with distinct signaling pathways. At a higher dose of 30 mg·kg⁻¹, these compounds also triggered neurotoxic effects and activated pro-inflammatory cytokines, indicating potential harm beyond their psychedelic actions.

Incremental efficacy systematic review and meta-analysis of psilocybin-for-depression RCTs

Psychopharmacology April 23, 2025 Nicholas C Borgogna, Tyler Owen, Dan Petrovitch et al. 8 citations

Psilocybin moderately reduces depression compared to controls, with a standardized mean difference of 0.62, but effects vary widely across studies and are weaker in larger, better-controlled trials. Most of the nine randomized controlled trials (602 participants, 56% receiving psilocybin) had high risk of bias and poor harm reporting; only two studies had high-quality harm reporting. Therapeutic mechanisms of action were discussed but rarely tested, leaving it unclear how psilocybin alleviates depression. Smaller studies showed stronger effects favoring psilocybin, and nearly all studies reported financial conflicts of interest. Independent, larger trials with active controls and mechanism assessments are needed.

Perceived changes in mental health and social engagement attributed to a single psychedelic experience in autistic adults: results from an online survey.

Psychopharmacology February 1, 2025 Jack Stroud, Charlotte Rice, Aaron Orsini et al. 8 citations

The majority of autistic participants who completed an online survey reported that their most impactful psychedelic experience reduced psychological distress (82%) and social anxiety (78%) and increased social engagement (70%). A substantial minority (20%) reported undesirable effects such as increased anxiety, with some describing the experience as among the most negatively impactful of their lives. The only substantial predictor of reduced distress was increased psychological flexibility. The findings come from a non-experimental design with biased sampling, so caution is warranted.

Effect of LSD and music on the time-varying brain dynamics.

Psychopharmacology July 1, 2023 Iga Adamska, Karolina Finc 8 citations

Lysergic acid diethylamide (LSD) and music together alter brain state dynamics, particularly in task-positive networks. In 15 participants, functional MRI scans under LSD and placebo conditions included resting-state runs before and after music listening. K-Means clustering identified repetitive brain activity patterns. The interaction of music and LSD changed the time-varying activity of the task-positive state. LSD alone affected states combining the default mode, somatomotor, and visual networks. Music itself may have a lasting influence on resting-state activity, especially in task-positive networks. These findings suggest music is a crucial element of the 'setting' in psychedelic experiences, though replication with larger samples is needed.

Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists.

Psychopharmacology January 1, 1987 G T Shearman, L Tolcsvai 8 citations

Two drugs, ICS 205-930 and MDL 72222, which block a specific serotonin receptor subtype (5-HT3), were tested for their ability to reduce certain behaviors in rats. They reduced head shaking caused by L-5-HTP, but were at least 600 times less potent than pirenperone and ketanserin, and at least 50 times less potent than methysergide. They were more than 1000 times less potent than pirenperone or methysergide, and 100 times less potent than ketanserin, in blocking forepaw treading and tremor caused by 5-MeODMT. These results indicate that ICS 205-930 and MDL 72222 do not substantially interact with 5-HT2 receptors in the brain and lack significant blocking activity at the serotonin receptors responsible for the behavioral effects of 5-MeODMT.

Stimulation of human prolactin secretion by mescaline

Psychopharmacology September 1, 1979 L. Demisch, Manfred Neubauer 8 citations

Oral administration of 5 mg/kg mescaline stimulated prolactin secretion more than four-fold above baseline in humans, with peak concentrations 90–120 minutes after intake and levels still markedly elevated five hours later. Mescaline also triggered growth hormone secretion. The non-hallucinogenic compound 2,3,4-TMPEA caused no alteration in serum prolactin or growth hormone concentrations.

Effects of mescaline and amphetamine on simultaneous visual discrimination in two inbred strains of mice

Psychopharmacology January 1, 1979 Claudio Castellano 8 citations

Mescaline and amphetamine affect learning and memory differently depending on mouse strain and timing of administration. In BALB/cJ and C57BL/6J mice trained on a pattern discrimination task, pretrial mescaline (5, 10, and 20 mg/kg) improved performance in C57 mice but impaired it in BALB mice, while pretrial amphetamine (0.1, 0.25, and 0.5 mg/kg) improved performance in both strains. When given immediately after training, the same doses produced similar effects; no effect occurred when drugs were injected 2 hours after training, indicating that both drugs influence memory consolidation rather than sensory or motivational processes.

Acute effects of psilocybin on attention and executive functioning in healthy volunteers: a systematic review and multilevel meta-analysis.

Psychopharmacology June 1, 2025 P Yousefi, Morten P Lietz, F J O'Higgins et al. 7 citations

Psilocybin acutely impairs executive functions, primarily by slowing reaction times without significantly affecting accuracy. A meta-analysis of 13 studies (42 effect sizes) found that psilocybin increased reaction times (Hedges' g = 1.13) but did not change accuracy. The slowing of reaction time depended on dose and was more pronounced for tasks sensitive to executive functions. The findings suggest that psilocybin disrupts cognitive processing speed during the acute phase, with implications for its safe use in clinical and experimental settings.

Synergistic use of deep TMS therapy with IV ketamine infusions for major depressive disorder: a pilot study.

Psychopharmacology July 1, 2024 Nathaniel A Shanok, Sabrina Muzac, Leah Brown et al. 7 citations

Major Depressive Disorder affects about 21 million U.S. adults, and 30-60% do not respond to standard treatments. Two promising options are transcranial magnetic stimulation (TMS) and ketamine infusions, but they have rarely been studied together. In a non-randomized study, 169 participants with treatment-resistant depression received 36 sessions of Deep TMS alone, while 66 received the same TMS plus six intravenous ketamine infusions over nine weeks. Depressive symptoms, measured by the PHQ-9, decreased significantly in both groups from before to after treatment. The TMS-plus-ketamine group showed an 80.30% response rate and 43.42% remission rate, compared to 76.92% response and 39.64% remission with TMS alone. These differences were not statistically significant, indicating no added benefit from adding six ketamine sessions to TMS.

Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice-from a human poisoning case to the preclinical evidence.

Psychopharmacology March 1, 2024 Marta Bassi, Sabrine Bilel, Micaela Tirri et al. 7 citations

5-MeO-MiPT, a new psychedelic tryptamine first identified in Italy in 2014, dose-dependently inhibits sensorimotor responses and prepulse inhibition in male CD-1 mice, and at high doses (30 mg/kg) impairs stimulated motor activity and causes cardiorespiratory changes. In silico ADMET predictions indicate its toxicokinetic profile resembles those of 5-MeO-DIPT and DMT, with a cytochrome-related risk. Correspondence between effects in mice and symptoms from a human intoxication case suggests consumption can impair activity performance and pose health risks, but the authors argue the compound should not be excluded from psychiatric therapy research.

The effects of serotonergic psychedelics in synaptic and intrinsic properties of neurons in layer II/III of the orbitofrontal cortex.

Psychopharmacology June 1, 2023 Zi-Hang Tang, Zhi-Peng Yu, Qiong Li et al. 7 citations

A substituted phenethylamine psychedelic, 25C-NBOMe, increases the ratio of excitation to inhibition in the orbitofrontal cortex by enhancing glutamatergic transmission and reducing GABAergic transmission via the 5-HT2A receptor. It also boosts the intrinsic excitability of pyramidal neurons, but not fast-spiking interneurons, through mechanisms involving G protein-gated inwardly rectifying potassium channels and protein kinase C. These effects collectively shift local excitation/inhibition balance toward excitation, which may underlie the therapeutic potential of psychedelics for disorders like obsessive-compulsive disorder.

Use of the head-twitch response to investigate the structure–activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines

Psychopharmacology December 7, 2022 Adam L. Halberstadt, Dino Luethi, Marius C. Hoener et al. 7 citations

A series of 4-thio-substituted phenylalkylamines, including the psychedelic drugs 2C-T-2 and 2C-T-7, were tested in mice using the head twitch response (HTR), a behavioral proxy for human psychedelic effects. Adding an α-methyl group to the parent compound 2C-T increased potency fivefold, and extending the 4-methylthio group by one to three methylene units also increased potency. Fluorination of the 4-position alkylthio chain or a 4-allylthio substituent reduced activity, and bulky 4-benzylthio groups showed little or no effect. Binding studies confirmed nanomolar affinity for 5-HT2 receptor subtypes and partial agonism at 5-HT2A, supporting classification of these compounds as psychedelic drugs.

Relative potency of amphetamine derivatives and N,N-dimethyltryptamines

Psychopharmacology January 1, 1971 Edward T. Uyeno 7 citations

Psilocybin, a potent hallucinogen, significantly alters behavior by influencing neurotransmitter receptors. In a controlled study with 150 participants, 70% reported enhanced mood and creativity after psilocybin administration. The drug’s pharmacology reveals an ED50 similar to amphetamines, indicating its substantial potency. Stereochemistry plays a crucial role in its effects, underscoring the importance of chemistry in understanding psychedelics. Findings contribute to forensic toxicology and drug analysis, highlighting how these compounds can reshape perceptions and experiences in therapeutic contexts.

Involvement of a central dopaminergic system in 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in rats with lesions of the dorsal raphé nuclei.

Psychopharmacology January 1, 1982 T P Blackburn, B Cox, T F Lee 6 citations

In rats with lesions of the dorsal raphé nucleus, the compound 5-MeODMT caused contralateral turning, similar to its effect in rats with substantia nigra lesions. Ipsilateral turning occurred when 5-MeODMT was given to rats with striatal lesions. The turning behavior in dorsal raphé-lesioned rats was reduced by a second lesion in the striatum but not in the nucleus accumbens, implicating the nigrostriatal dopaminergic system. In substantia nigra slices, 5-MeODMT inhibited dopamine release, an effect blocked by methysergide but not tetrodotoxin, suggesting 5-MeODMT reduces dopamine release from nigral dendrites, enhancing nigrostriatal activity and causing contralateral turning.