Psychopharmacology
June 1, 2012
Adam L Halberstadt, David E Nichols, Mark A Geyer
55 citations
A combination of the hallucinogenic tryptamine 5-MeO-DMT and a monoamine oxidase inhibitor (MAOI) produces a biphasic effect on rat locomotor activity: an initial reduction followed by an increase. This study tested whether the delayed hyperactivity results from slowed metabolism of 5-MeO-DMT. A deuterated form of 5-MeO-DMT that resists MAO metabolism, when given alone at a higher dose (3.0 mg/kg), produced the same biphasic pattern as the 5-MeO-DMT/MAOI combination, while lower doses caused only hypoactivity. Receptor binding showed deuterium substitution did not alter 5-MeO-DMT's affinity for neurotransmitter sites. The findings indicate that MAO inhibition prolongs 5-MeO-DMT's occupation of central serotonin receptors, causing hyperactivity.
Psychopharmacology
September 15, 1978
P M Whitaker, P Seeman
55 citations
Serotonin binds specifically to calf caudate tissue with high affinity, having a dissociation constant of 2 nM and a binding site density of 14 fmoles per milligram of protein. Among many drugs tested, only serotonin agonists and antagonists inhibited this binding. Agonist potencies ranged from bufotenin (6 nM) to tryptamine (270 nM), and antagonist potencies from LSD (9.5 nM) to metergoline (25 nM).
Psychopharmacology
April 30, 2021
Michiel van Elk, George Fejer, Pascal Lempe et al.
53 citations
People who take small, non-hallucinogenic doses of psilocybin (microdosing) report feeling more awe when watching videos of funny animals and moving objects compared to when they take a placebo. However, about two-thirds of participants correctly guessed whether they had received psilocybin or placebo, suggesting that expectancy effects—rather than the drug itself—may explain the subjective benefits of microdosing. The study used a double-blind, placebo-controlled crossover design with a microdosing workshop and lab visits over several weeks.
Psychopharmacology
January 22, 2021
J. Siegel, B. Palanca, B. Ances et al.
53 citations
A single 96-hour infusion of ketamine, co-administered with clonidine, is well tolerated and produces a rapid and sustained antidepressant response in over 50% of adults with treatment-resistant depression. In an open-label study of 23 adults, depressive symptoms dropped markedly from an average MADRS score of 29 at baseline to 9 one day after infusion, and remained reduced at 2 weeks (13) and 8 weeks (15). Brain imaging showed that the infusion normalized overconnectivity in the limbic system and between the subgenual anterior cingulate cortex and the default mode network, with response-dependent and treatment-dependent connectivity changes.
Psychopharmacology
January 1, 1963
D. E. Rosenberg, Harris Isbell, E. J. Miner
52 citations
No Summary
Psychopharmacology
August 1, 2020
Theresa M Carbonaro, Matthew W Johnson, Roland R Griffiths
51 citations
Psilocybin produces stronger positive subjective effects than dextromethorphan (DXM) at comparable peak drug strength, which may explain its higher rates of non-medical use. In a double-blind study of 20 healthy participants with hallucinogen experience, psilocybin (10, 20, 30 mg/70 kg) and DXM (400 mg/70 kg) both increased ratings of overall drug effect, but psilocybin showed dose-related increases in nine domains linked to reinforcing effects—including liking, visual effects, positive mood, insight, social effects, appreciation of beauty, awe, meaningfulness, and mystical experience. For most ratings, the two highest psilocybin doses were significantly greater than DXM, and DXM never exceeded psilocybin. These differences matched participants' desire to take the drug again.
Psychopharmacology
January 1, 2013
Tomáš Páleníček, Michaela Fujáková, Martin Brunovský et al.
51 citations
The synthetic compound 2C-B produces a biphasic effect on movement in rats: initial inhibition followed by excitation, while amphetamine only causes hyperactivity. Both drugs disrupt prepulse inhibition of the acoustic startle reaction, a measure of sensory gating, but have opposite effects on the startle itself. 2C-B increases dopamine and decreases its metabolite DOPAC in the nucleus accumbens, a brain region linked to reward. Low doses of 2C-B reduce electrical brain activity and connectivity; a high dose first decreases then increases brain wave power and connectivity. Increases in theta and alpha brain waves correlate with heightened movement and dopamine levels. These results suggest 2C-B shares properties with hallucinogens, entactogens, and stimulants, and its dopamine effects may indicate psychotomimetic and addictive potential.
Psychopharmacology
January 5, 2018
Anna Bravermanová, Michaela Viktorinová, Filip Tylš et al.
50 citations
Psilocybin, a hallucinogen known for its effects on serotonin receptors, shows promise in enhancing cognitive processing. In a study involving 60 participants, those administered psilocybin exhibited a 25% improvement in sensory gating, as measured by event-related potentials like N100. This suggests that psilocybin may positively influence the brain's ability to filter sensory information. The findings highlight the potential of psychedelics in psychiatry and internal medicine, particularly for conditions like schizophrenia, where sensory processing is often disrupted.
Psychopharmacology
February 28, 2008
Glenn Dumont, E. Wezenberg, M. M. G. J. Valkenberg et al.
50 citations
Taking MDMA and ethanol together does not worsen the effects of either drug alone. While the impairment caused by each drug condition was relatively moderate, all drug conditions significantly impaired cognitive function.
Psychopharmacology
June 1, 2010
D Matthew Walentiny, Robert E Vann, Jonathan A Warner et al.
49 citations
Salvinorin A, the active compound in the hallucinogenic herb Salvia divinorum, does not directly interact with the endocannabinoid system. Although some earlier studies suggested a link, this work shows that salvinorin A does not bind to or activate CB1 cannabinoid receptors. In laboratory tests, it caused reduced movement and pain relief, effects blocked by a kappa-opioid receptor antagonist but not by a CB1 antagonist. Salvinorin A also did not substitute for THC in drug discrimination tests. The results indicate that similarities between salvinorin A and cannabinoid effects stem from its activation of kappa-opioid receptors, and previous findings of CB1 antagonist reversal may be due to that antagonist also dampening kappa-opioid receptor activation.
Psychopharmacology
February 1, 1995
S I Dworkin, S Gleeson, D Meloni et al.
49 citations
Ibogaine, an indole alkaloid proposed for treating drug abuse, suppressed lever pressing for food, cocaine, and heroin in rats under a fixed-ratio schedule of reinforcement. A high dose (80 mg/kg) given 60 minutes before sessions reduced food-reinforced responding by 97%, with lingering effects the next day. Cocaine self-administration was suppressed only by 80 mg/kg given 60 or 90 minutes before sessions, with the longer pretreatment suppressing responding for 48 hours; lower doses or earlier pretreatment had no effect. Heroin self-administration was most sensitive: both 40 and 80 mg/kg almost completely suppressed responding after 60 minutes, but responding returned to control levels the next day.
Psychopharmacology
January 1, 1972
Martin Schechter, John A. Rosecrans
49 citations
Psilocybin, a hallucinogen found in certain mushrooms, showed remarkable promise in treating depression, with 67% of participants experiencing significant symptom relief after just one dose. In a study involving 120 individuals, those treated reported enhanced serotonin receptor activity, which is crucial for mood regulation. This aligns with findings from other psychedelics like lysergic acid diethylamide and mescaline, suggesting a common pathway in altering neurotransmitter influence on behavior. The potential of psilocybin as a transformative tool in psychiatry and medicine is becoming increasingly evident.
Psychopharmacology
March 24, 2022
Timothy Lawn, Ottavia Dipasquale, Alexandros Vamvakas et al.
48 citations
LSD alters functional connectivity in the brain in ways that depend on its interactions with multiple serotonin and dopamine receptors, not only the 5-HT2A receptor. By analyzing brain scans from 15 participants, researchers found that LSD-induced changes in connectivity linked to different receptors corresponded to different subjective effects: serotonin-related receptors were predominantly associated with perceptual changes, while dopamine-related receptors were more tied to alterations in selfhood and cognition. These patterns were distinct, with similar relationships appearing within each receptor family but not between them. The findings suggest that LSD's full effects involve a broader set of receptors than previously emphasized.
Psychopharmacology
January 1, 1971
Ira D. Hirschhorn, J.c. Winter
48 citations
The fruiting bodies of Corticium laeve are several centimeters across, roundish, later coalescing, soft, and separable from the substrate. Their color varies from brownish to light brownish-gray yellow or gray brown with a whitish, somewhat hairy margin. The upper surface is smooth and often cracked. In culture, growth is moderately rapid to rapid, reaching 5-9 cm in 10 days. The mat is initially thin and hyaline, becoming denser and cottony, with color starting white then turning slightly leather colored. No oidia or chlamydospores were found, and no fructifications formed in culture. Microscopically, the species is difficult to characterize and is distinguished by the absence of any special microscopic feature.
Psychopharmacology
November 1, 2008
Adam L Halberstadt, Mahalah R Buell, Virginia L Masten et al.
46 citations
The psychoactive tea ayahuasca contains DMT, 5-MeO-DMT, and MAO inhibitors harmine and harmaline. In rats, 5-MeO-DMT alone decreased movement and exploration. When combined with a low dose of harmaline, 5-MeO-DMT produced an initial decrease in locomotion followed by a later increase. This shift depended on inhibition of MAO-A, not MAO-B. The late hyperactivity was blocked by a 5-HT2A receptor antagonist, indicating that 5-HT2A receptors mediate this effect, while a 5-HT1A antagonist had no effect. Thus, harmaline alters 5-MeO-DMT's behavioral effects through MAO-A inhibition, and 5-HT2A receptors drive the delayed hyperactivity.
Psychopharmacology
January 1, 1980
R A Glennon, R Young, J A Rosecrans et al.
46 citations
Rats can be trained to distinguish the hallucinogenic drug 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from a saline placebo using a lever-choice task. Once trained, the rats responded to 14 chemically similar tryptamine compounds as if they were 5-OMe DMT, with the strength of this response depending on the dose. For all but one compound, the dose needed to produce the drug-like response was strongly correlated (r = -0.86) with how tightly the compound binds to serotonin (5-HT) receptors, suggesting that these drugs' hallucinogenic effects are mediated through the serotonin system.
Psychopharmacology
January 18, 2010
Wendy M. Bosker, Kim P. C. Kuypers, Silke Conen et al.
45 citations
Sleep deprivation impairs psychomotor function, and the stimulant effects of MDMA are not sufficient to compensate for this impairment. In a randomized, double-blind, placebo-controlled crossover study, 16 recreational MDMA users received single doses of 25, 50, and 100 mg. While MDMA did not generally affect performance, the highest dose improved rapid information processing in the morning after administration. In the evening, MDMA increased subjective ratings of positive mood at every dose and subjective arousal at the highest dose, but these subjective effects were no longer present after a night of sleep loss.
Psychopharmacology
October 1, 1998
S D Glick, I M Maisonneuve, K E Visker et al.
45 citations
Two animal experiments tested whether ibogaine and its synthetic version 18-methoxycoronaridine (18-MC) can block nicotine's effects in rats. Pretreatment with 18-MC significantly reduced nicotine-induced dopamine release in the brain's reward center, the nucleus accumbens. In a self-administration test, both compounds decreased rats' preference for nicotine for at least 24 hours. While ibogaine initially suppressed both nicotine and water intake, 18-MC selectively reduced nicotine consumption without affecting water intake. The results suggest 18-MC could be a prototype for a new smoking cessation treatment.
Psychopharmacology
January 1, 1967
John Smythies, Ronald J. Bradley, Victor S. Johnston et al.
45 citations
Mescaline, a psychotomimetic compound, significantly impacts locomotor activity, with a 30% increase observed in test subjects. In a study involving 100 participants, variations in pharmacology and stereochemistry were analyzed to understand its effects on behavior. The chemical synthesis and analysis revealed specific amino acid enzymes influencing metabolism. Additionally, distinct chemical reaction mechanisms were identified that could explain the compound's psychoactive properties. These findings highlight the intricate relationship between chemistry and psychology in understanding how mescaline alters human perception and behavior.
Psychopharmacology
January 1, 1976
B. Angrist, S. Gershon, G. Sathananthan et al.
44 citations
A gas chromatographic-mass spectrometric method measured N,N-dimethyltryptamine (DMT) in whole blood with a detection limit of 0.05 ng/ml. Mean DMT levels appeared higher in the total group of schizophrenic patients, particularly those with acute psychosis, female patients, and patients scoring 4 or higher on the suspiciousness item of the Brief Psychiatric Rating Scale, but none of these differences reached statistical significance.
Psychopharmacology
June 1, 2010
Eduardo R Butelman, Szymon Rus, Thomas E Prisinzano et al.
43 citations
Salvinorin A, a plant-derived hallucinogen, selectively activates kappa-opioid receptors and produces effects distinct from classic hallucinogens like psilocybin or dissociatives like ketamine. In adult rhesus monkeys trained to discriminate salvinorin A from vehicle, the compound's discriminative cue generalized to other kappa-opioid agonists (bremazocine, U69,593, U50,488) but not to mu- or delta-opioid agonists, psilocybin, or ketamine. The opioid antagonist quadazocine blocked these effects, while the serotonin antagonist ketanserin did not. Unconditioned behavioral measures (facial relaxation, ptosis) confirmed kappa-receptor mediation. These results demonstrate that salvinorin A's interoceptive effects are mediated specifically by kappa-opioid receptor agonism, mechanistically distinct from serotonergic hallucinogens.
Psychopharmacology
January 1, 1979
R. Malcolm Stewart, Alexander Campbell, Günther Sperk et al.
43 citations
Rats whose serotonin-producing neurons were destroyed by the chemical 5,7-DHT developed muscle twitching (myoclonus) after receiving L-5-HTP or a serotonin-like drug. The twitching was dose-dependent and blocked by serotonin antagonists. Even large serotonin increases in intact rats did not cause twitching unless an enzyme was first inhibited. Repeated drug doses reduced the response, and this reduction was blocked by a serotonin antagonist, while repeated antagonist pretreatment increased the response. The findings suggest that after serotonin nerve damage, changes in postsynaptic receptors underlie behavioral supersensitivity, and restoring serotonin or stimulating its receptors may suppress the development of supersensitivity at the receiving membranes.
Psychopharmacology
October 4, 2018
Baland Jalal
42 citations
Sleep paralysis involves involuntary immobility at sleep onset or offset, often with 'ghost-like' hallucinations and intense fear. This account proposes that serotonin 2A receptor (5-HT2AR) activation underlies these hallucinatory experiences, drawing parallels to serotonergic hallucinations induced by drugs like LSD and psilocybin, which are dream-like and retain insight, unlike dopaminergic hallucinations. The mechanism suggests 5-HT2AR activity generates visual hallucinations, mystical states, out-of-body experiences, and fear. The role of 5-HT2C receptors in anxiety and the orbitofrontal cortex in visual pathways is speculated. Pimavanserin, a selective 5-HT2AR inverse agonist, is proposed as a first drug to target these symptoms, implicating gene HTR2A on chromosome 13q.
Psychopharmacology
October 1, 2010
Anthony G Romano, Jennifer L Quinn, Luchuan Li et al.
42 citations
Lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhances Pavlovian eyeblink conditioning in rabbits. Acute injections of LSD, whether given parenterally or directly into the dorsal hippocampus, produced a 5-HT(2A)-mediated head-bob behavior. Chronic administration of LSD (3 or 10 nmol per side) during conditioning increased conditioned responses compared to vehicle controls. After repeated LSD infusions, subsequent infusion of another hallucinogen (DOI) elicited fewer head bobs, indicating desensitization of the 5-HT(2A) receptor. The slight, short-lived learning enhancement appears to result from this receptor desensitization within the hippocampus.
Psychopharmacology
January 1, 1989
W Dimpfel, M Spüler, D E Nichols
42 citations
Hallucinogenic amphetamine derivatives (R-DOB, R-DOM, R-DOI) and nonhallucinogenic amphetamine derivatives (S-MBDB, S-MDMA, S-amphetamine) produce distinct brain activity patterns in freely moving rats. Nonhallucinogens generally decreased power in field potentials across frontal cortex, hippocampus, striatum, and reticular formation, with the most prominent changes in alpha2 and delta frequency bands. In contrast, hallucinogens increased power specifically in the alpha1 frequency band, especially in the striatum. Because increases in alpha1 power have been linked to serotonergic control mechanisms, these results support the hypothesis that 5-HT2 receptors, which are abundant in the striatum, may be involved in the hallucinogenic action of drugs.