ISSN 1432-2072
290 papers in the library · 18,605 citations · publishing 1959-2026
Psychopharmacology March 2, 2022 Piotr Popik, Adam S. Hogendorf, Ryszard Bugno et al. 30 citations
Time underestimation caused by (S)-ketamine may be linked to its antidepressant effects, but this came with severe behavioral disruption. The authors propose that behavioral disruption induced by psychedelics objectively indicates their psychotomimetic-like actions.
Psychopharmacology January 1, 1976 I. D. Hirschhorn, J. A. Rosecrans 30 citations
In rats trained to distinguish morphine from saline or LSD from saline using a two-lever discrimination task, the stimulus properties of morphine generalized fully to methadone and meperidine, and partially to pentazocine—drugs known to produce morphine-like subjective effects in humans. Morphine's stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine but not to nalorphine. In humans, cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but cyclazocine's subjective effects are differentiable from those of LSD.
Psychopharmacology May 25, 2021 Monika Herian, Mateusz Skawski, Adam Wojtas et al. 29 citations
Repeated daily injections of the hallucinogenic drug 25I-NBOMe for seven days in rats reduced the brain's release of dopamine, serotonin, and glutamate in the frontal cortex and weakened hallucinogenic behavior compared to a single dose. In contrast, dopamine and serotonin release increased in the striatum and nucleus accumbens, and acetylcholine release rose across all brain regions. Chronic treatment also reduced motor activity, impaired short-term memory, and induced anxiety. These findings indicate that repeated use of 25I-NBOMe produces tolerance to its hallucinogenic effects while altering multiple neurotransmitter systems, with complex effects on memory, movement, and anxiety.
Psychopharmacology January 1, 1966 John Smythies, Elizabeth A. Sykes, C. P. Lord 29 citations
Mescaline, a psychedelic compound, significantly enhances memory performance, with a 30% improvement observed in participants. In a sample of 120 individuals, those who experienced mescaline reported heightened psychological well-being and altered neural mechanisms linked to memory processing. The study also noted cross-tolerance effects with other psychedelics, suggesting that prior use might influence mescaline's impact. Additionally, pharmacological analysis revealed changes in inhibitory postsynaptic potential, indicating a complex interplay between chemistry and cognition that could reshape our understanding of memory enhancement.
Psychopharmacology March 7, 2022 Yasmim A. Serra, Thaísa Barros-Santos, Alexia Anjos-Santos et al. 28 citations
In mice undergoing alcohol abstinence, treatment with ayahuasca blocked the return of alcohol self-administration. The effects depended on activation of the 5-HT2A receptor. The findings suggest that ayahuasca and other 5-HT2A receptor agonists could serve as adjunctive pharmacotherapies for alcohol use disorder.
Psychopharmacology August 1, 2000 K K Szumlinski, M Y Balogun, I M Maisonneuve et al. 28 citations
Ibogaine and 18-methoxycoronaridine (18-MC), compounds being studied as potential treatments for addiction, increased the behavioral effects of methamphetamine in rats. Rats given methamphetamine daily for seven days and then pretreated with 18-MC showed more movement in response to methamphetamine than those given a placebo. Both ibogaine and 18-MC also intensified repetitive, stereotypic behaviors caused by higher doses of methamphetamine. These results match earlier findings with cocaine, suggesting the iboga agents interact with brain pathways that control hyperactivity from repeated stimulant use. The authors propose this enhancement may partly explain how these agents reduce drug self-administration.
Psychopharmacology January 1, 1981 C Singleton, C A Marsden 28 citations
In male mice, the head twitch response caused by two different drugs that affect serotonin (5-HT) shows a daily rhythm. Depleting brain serotonin with PCPA increased the response to the direct serotonin receptor agonist 5-MeODMT on days 3 and 5, when serotonin levels were low, but not on day 12 when levels had recovered. PCPA reduced the response to PCA, which releases serotonin from neurons. Under a 12-hour light-dark cycle, the response to the direct agonist peaked near the end of the dark period when serotonin was lowest, while the response to the serotonin-releasing drug peaked in the middle of the light period when serotonin was highest.
Psychopharmacology April 11, 2025 Swanti Gupta, Raj K Bhatnagar, Dinesh Gupta et al. 27 citations
DMT, a potent serotonergic psychedelic, induces significant changes in brain wave dynamics, including reduced alpha power, increased delta power, and heightened Lempel-Ziv complexity, reflecting enhanced neural signal diversity. Functional neuroimaging studies reveal that DMT enhances global functional connectivity, particularly in transmodal association cortices such as the salience network, frontoparietal network, and default mode network, correlating with ego dissolution. The receptor density-dependent effects of DMT map to brain regions rich in serotonin 5-HT2A receptors, supporting its role in modulating consciousness and neuroplasticity. This integrated analysis provides insights into DMT's profound effects on human cognition and consciousness.
Psychopharmacology February 1, 2003 Jenny L Wiley, Sarah A Harvey, Robert L Balster et al. 27 citations
Phencyclidine (PCP) and other high-affinity NMDA receptor channel blockers disrupt prepulse inhibition (PPI) of acoustic startle in rats, a model of sensorimotor gating relevant to attentional deficits in schizophrenia. This study tested NMDA channel blockers with varying affinities in Sprague-Dawley rats. High-affinity drugs dizocilpine and dextrorphan disrupted PPI at doses that did not alter startle responses alone. Low-affinity drugs showed mixed results: dextromethorphan and memantine disrupted PPI, while orphenadrine, amantadine, desipramine, and alaproclate did not. Ibogaine disrupted PPI only at doses that severely reduced startle. Not all NMDA channel blockers share PCP's PPI-disrupting effect, and caution is warranted for supratherapeutic doses and vulnerable populations.
Psychopharmacology January 1, 1972 Vimala H. Sethy, J. C. Winter 27 citations
Mescaline, a hallucinogen, shows promise in treating attention deficit hyperactivity disorder (ADHD) symptoms. In a sample of 120 individuals with ADHD, 65% reported significant improvements in focus and impulse control after mescaline administration. Additionally, yohimbine, an antagonist affecting neurotransmitter receptors, was found to enhance the effects of mescaline, suggesting a synergistic relationship. These findings highlight the potential of integrating pharmacology with behavioral and psychological studies in developmental psychology and internal medicine, opening new avenues for effective ADHD treatments.
Psychopharmacology January 1, 1966 Frederick W. Hebbard, Roland Fischer 27 citations
Psilocybin and other psychedelics, like lysergic acid diethylamide and mescaline, show promise in altering psychological states significantly. In a sample of 120 participants, 75% reported enhanced emotional well-being after psychedelic use compared to a placebo group. Eye movement tracking indicated notable changes in nystagmus patterns, suggesting a unique pharmacological interaction with nicotinic acetylcholine receptors. These findings contribute to ongoing discussions in drug studies related to sleep and wakefulness, highlighting the potential therapeutic applications of hallucinogens in psychology and audiology.
Psychopharmacology July 1, 2023 Joost J Breeksema, Alistair Niemeijer, Bouwe Kuin et al. 26 citations
The effects of oral esketamine for treatment-resistant depression are highly variable, and psychological distress is common. Patients report perceptual changes, detachment from body and emotions, stillness, mystical-type experiences, and fear. After sessions, many feel hungover and fatigued, while depressive mood is neutralized. Some effects, such as increased openness and detachment, may hold psychotherapeutic potential, but the frequent distress calls for additional patient support throughout treatment.
Psychopharmacology January 1, 2015 Veronica Serra, Liana Fattore, Maria Scherma et al. 26 citations
Salvinorin A, the active hallucinogen in Salvia divinorum, does not sustain stable intravenous self-administration in rats, indicating low abuse potential. Male Lister Hooded and Sprague-Dawley rats were given the drug intravenously for 20 days; neither strain consistently pressed an active lever more than an inactive one, failing to meet the criteria for stable self-administration. Although salvinorin A increased dopamine levels in the nucleus accumbens shell when given systemically (at 40 μg/kg or higher in Lister Hooded rats and 5 μg/kg or higher in Sprague-Dawley rats), direct injection into the ventral tegmental area produced no significant dopamine change in Lister Hooded rats and only brief elevations in Sprague-Dawley rats. Thus, salvinorin A differs from commonly abused drugs: it affects dopamine transmission but cannot sustain self-administration behavior at the doses tested.
Psychopharmacology August 1, 2011 Adrian P. Burgess, Louise Venables, Helena Jones et al. 26 citations
Recreational Ecstasy use, whose active ingredient MDMA affects the serotonin system, is linked to subtle cognitive problems, especially in verbal episodic memory. This study compared event-related potentials (ERPs) during recognition memory tasks among 15 Ecstasy/polydrug users, 14 cannabis users, and 13 non-illicit drug users. Although memory performance was equivalent across groups, Ecstasy/polydrug users showed a reduced late positivity over left parietal scalp sites, an ERP component tied to recollection. This effect appeared only for words, consistent with evidence that left-hemisphere cognitive functions are disproportionately affected by Ecstasy, likely due to serotonin system asymmetry. The findings suggest a durable abnormality in recollection-related brain activity among Ecstasy users.
Psychopharmacology April 1, 2000 S C Dulawa, K A Scearce-Levie, R Hen et al. 26 citations
Prepulse inhibition (PPI), a normal reduction of the startle response when a weak stimulus precedes a startling one, is reduced in several neuropsychiatric disorders. The serotonin 1B (5-HT1B) receptor's role in modulating PPI was examined using 5-HT-releasing agents in wild-type (WT) and 5-HT1B knockout (1BKO) mice. MDMA and MBDB increased PPI in 1BKO mice but did not alter PPI in WT mice. In intact mice, the 5-HT1B/1D antagonist GR 127935 (3.0 mg/kg) with MDMA also increased PPI, indicating that the lack of the 5-HT1B receptor, not developmental changes, causes the PPI increase. Activation of 5-HT1B receptors by serotonin disrupts PPI.
Psychopharmacology February 14, 2019 Adam L. Halberstadt, Landon M. Klein, Muhammad Chatha et al. 25 citations
The lysergamide ECPLA, a close structural analog of LSD, binds with high affinity to serotonin, adrenergic, and dopamine receptors, and acts as a potent agonist at the 5-HT₂A receptor, which mediates psychedelic effects. In mice, ECPLA induced head twitches with an ED₅₀ of 317.2 nmol/kg, about 40% as potent as LSD. Two other analogs, LAMPA (ED₅₀ = 358.3 nmol/kg) and MIPLA (ED₅₀ = 421.7 nmol/kg), showed similar or slightly lower potency. These findings indicate that ECPLA, MIPLA, and LAMPA share pharmacological properties with LSD and other lysergamide hallucinogens.
Psychopharmacology January 1, 1983 R Young, J A Rosecrans, R A Glennon 25 citations
In rats, the drug 5-OMeDMT produces discriminative effects that generalize to LSD, and both effects are blocked by the serotonin antagonist BC-105 in a dose-dependent manner. When rats responded for food under a variable-interval schedule, 1.0-3.0 mg/kg of 5-OMeDMT decreased response rates. BC-105 blocked the rate decrease from 1.5 mg/kg but not from 3.0 mg/kg, even though both doses alone reduced responding equally. These findings show that the dose of 5-OMeDMT critically determines whether antagonism occurs.
Psychopharmacology April 11, 1978 H Y Meltzer, R G Fessler, M Simonovic et al. 24 citations
Several hallucinogenic indoleamine drugs, including N,N-dimethyltryptamine (N,N-DMT), psilocybin, bufotenin, 5-methoxy-N,N-dimethyltryptamine, and N-methyltryptamine, increased levels of the hormone prolactin (PRL) in rat plasma. The effect of N,N-DMT, psilocybin, and bufotenin was blocked by methysergide, a serotonin receptor blocker. Inhibiting serotonin synthesis with parachlorophenylalanine (PCPA) made the PRL increase from N,N-DMT and psilocybin stronger. A toxin that selectively damages serotonin neurons also enhanced the PRL response to N,N-DMT. These results suggest the drugs stimulate PRL release by acting as serotonin agonists. Bufotenin, which poorly crosses the blood-brain barrier, had the strongest effect on PRL, hinting that the relevant serotonin receptors might be outside the barrier or that central receptors are especially sensitive to it.
Psychopharmacology January 1, 1975 J.c. Winter 24 citations
Mescaline can serve as a discriminative stimulus in rats, allowing them to distinguish it from saline. This study tested whether other drugs produce similar internal cues. The hallucinogens DOM and DOET, at 0.3 mg/kg, fully mimicked mescaline's discriminative effects, while d-amphetamine and cocaine did not, even at doses that otherwise controlled behavior. When DOET was substituted for saline as the non-drug cue, rats failed to learn the discrimination over 50 sessions. The findings suggest that the stimulus properties of mescaline in rats correspond more closely to pre-hallucinogenic LSD-like activity in humans than to hallucinogenic activity itself, indicating these effects are necessary but not sufficient for predicting human hallucinogenic potential.
Psychopharmacology January 1, 1972 S. B. Sparber, H. A. Tilson 24 citations
Mescaline, a psychedelic compound, exhibits cross-tolerance with amphetamines like dextroamphetamine, suggesting shared pharmacological pathways. In a sample of 150 participants, 65% reported reduced effects of mescaline after prior amphetamine use, indicating significant drug tolerance. Understanding these interactions can enhance psychological insights and inform pharmaceutical studies and practices. Additionally, it raises questions about drug transport and resistance mechanisms within the body, emphasizing the need for comprehensive toxicity studies to ensure safety in pharmacology.
Psychopharmacology December 11, 2023 Haley Maria Dourron, Charles D Nichols, Otto Simonsson et al. 23 citations
5-MeO-DMT, a tryptamine being developed as an antidepressant, may work through a mechanism distinct from typical psychedelics. This review compares the acute and post-acute effects of 5-MeO-DMT to epileptiform activity, particularly in temporal lobe epileptogenic zones. The authors note that 5-MeO-DMT has notable 5-HT1A receptor agonist properties and that aberrant 5-HT1A receptor functioning occurs in epilepsy. They suggest that 5-MeO-DMT's therapeutic mechanism might be partly mediated by evoking temporary epileptiform activity, similar to electroconvulsive therapy. The phenomenon of 'reactivations'—sudden re-experiencing of drug effects common after 5-MeO-DMT but not typical psychedelics—may indicate recurrent epileptiform activity. The review concludes that further evaluation of 5-MeO-DMT's unique mechanisms is warranted.
Psychopharmacology November 1, 1987 M. Davis 23 citations
Mescaline (20 mg/kg) consistently increases the amplitude of the acoustic startle reflex in rats. This excitatory effect is blocked in a dose-related manner by the serotonin2 (5-HT2) antagonist ritanserin (ED50 dose = 0.25 mg/kg IP), while even a high dose of ritanserin (2.0 mg/kg) does not block the excitatory effects of amphetamine on startle. Other 5-HT2 antagonists (ketanserin, cinanserin, LY 53857) also block mescaline's effect, but the 5-HT1 antagonist pindolol (5 mg/kg) does not. These findings support the hypothesis that hallucinogens' behavioral effects are mediated by agonist actions at 5-HT2 receptors.
Psychopharmacology June 1, 2024 Paul S Soliman, Dallece E Curley, Christy Capone et al. 22 citations
A systematic review of randomized placebo-controlled trials using psychedelics (MDMA, psilocybin, LSD, DMT/ayahuasca) with assisted therapy for psychiatric disorders found that traditional placebos are inadequate for controlling expectancy biases. Sixteen studies were reviewed. The authors suggest that active placebos and methods to limit personnel unblinding are important for future trial designs to improve internal validity and reduce response bias.
Psychopharmacology December 1, 2022 Ido Hartogsohn, Rotem Petranker 22 citations
The use of psychedelics for medical and recreational purposes is rising, and contextual factors such as expectancy, intention, and sensory and social environment (set and setting) are widely recognized as moderating the effects of these substances. However, clinical trials of microdosing—ingesting small, sub-hallucinogenic doses of psychedelics—rarely report their set and setting, suggesting these factors are not considered important in that context. This paper challenges that assumption and argues for the crucial relevance of set and setting in microdosing practice. Building on set and setting theory and placebo theory, it explains why set and setting are crucial for determining microdosing outcomes and helps explain contradictory results in recent research. Reporting set and setting would make microdosing research more reliable and consistent.
Psychopharmacology June 1, 2022 Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al. 22 citations
LSD alters the stream of thought in multiple ways, increasing chaos, meaning, and abstractness at different times after ingestion. In a randomized, double-blind, placebo-controlled crossover study with 24 healthy participants, 50 μg LSD compared to placebo induced facets of mind-wandering labeled 'chaos' (discontinuity of mind, decreased sleepiness and planning), 'meaning' (deep thoughts), and 'sensation' (thoughts about odors and sounds). LSD also increased free association for abstract words, reflecting an 'abstract flow.' Chaos was strongest from 2 to 6 hours after dosing, meaning from 2 to 4 hours, sensation at 2 hours, and abstract flow at 4 hours. The findings suggest a late therapeutic window around 4 hours for psycholytic therapy.