Skip to content

Psychopharmacology

ISSN 1432-2072

290 papers in the library · 18,605 citations · publishing 1959-2026

Papers

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.

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.

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.