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
July 22, 2017
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
24 citations
MDMA reduced the arousal normally elicited by negative sounds, and this effect was blocked by pre-treatment with ketanserin, a 5-HT2 receptor antagonist, indicating the involvement of the serotonin 2A receptor. The drug did not produce a bias toward emotional or social stimuli in the tasks used. MDMA increased both positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal to negative sounds was unrelated to subjective arousal levels. This decrease in defensive arousal may contribute to MDMA's therapeutic effects.
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.
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
January 26, 2021
Eef L. Theunissen, Johannes T. Reckweg, Nadia R. P. W. Hutten et al.
20 citations
A moderate dose of the synthetic cannabinoid JWH-018, inhaled by 24 healthy adults with no history of mental illness, produced pronounced psychedelic and dissociative effects, including altered perception, amnesia, derealization, depersonalization, and confusion. The average dose administered was 5.52 mg. These findings indicate that synthetic cannabinoids pose a serious risk for public health by inducing psychotomimetic symptoms even in people without prior mental health issues.
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
June 27, 2019
Lilian Kloft, Henry Otgaar, Arjan Blokland et al.
19 citations
Cannabis intoxication and a history of regular cannabis use are linked to a more liberal response criterion in memory tasks, leading to higher false recognition of unrelated items. In a field study using the Deese/Roediger-McDermott (DRM) paradigm, regular cannabis consumers who were acutely intoxicated (n = 53), regular cannabis consumers who were sober (n = 50), and cannabis-naïve controls (n = 53) completed a memory test. False memory rates for critical lures did not statistically differ between groups, but both intoxicated and sober cannabis consumers falsely recognized more unrelated items than controls. Cannabis-naïve individuals showed higher memory accuracy compared with the intoxicated group.
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.