Psychopharmacology
January 25, 2022
Felix Müller, Elias Kraus, Friederike Holze et al.
64 citations
Up to 9.2% of healthy volunteers reported reoccurring drug-like experiences after taking LSD or psilocybin in controlled studies, but none met the criteria for hallucinogen-persisting perception disorder (HPPD). The experiences were mostly mild, visual, brief, and perceived as neutral or pleasant, with no impairment in daily life. Distressing experiences occurred in two subjects but subsided spontaneously. The findings suggest that flashbacks are not a clinically relevant problem in controlled settings with healthy participants.
Psychopharmacology
September 1, 2020
Valerie Van Mulukom, Ruairi E Patterson, Michiel van Elk
61 citations
Classical serotonergic psychedelic (CSP) experiences that induce awe, but not ego dissolution, are linked to lower maladaptive narcissism through increased feelings of connectedness and affective empathetic drive. In a survey of 414 participants describing their most awe-inspiring psychedelic experience, those reporting more awe showed higher connectedness and empathy, which in turn predicted reduced exploitative-entitled narcissism. This relationship persisted after controlling for sensation-seeking. No evidence was found that ego dissolution produced the same effects. The findings suggest CSPs may have therapeutic potential for disorders involving deficits in connectedness and empathy, such as pathological narcissism, with awe-driven connectedness as a key mechanism.
Psychopharmacology
October 6, 2007
Tomáš Páleníček, Marie Balı́ková, Vĕra Bubeníková‐valešová et al.
61 citations
Mescaline, a nonselective serotonin receptor agonist, produced significant inhibitory effects on locomotion in rats at low doses and a biphasic effect at the highest dose. In tests of sensorimotor gating (prepulse inhibition of acoustic startle), all doses disrupted gating only when tested 60 minutes after administration. Approximately 50% of animals receiving 100 mg/kg died within 12 hours. Serum mescaline levels rose rapidly within 30 minutes and then quickly declined, while brain concentrations peaked 1 hour after administration and remained elevated for another 60 minutes. The delayed onset of behavioral changes correlated with the drug's pharmacokinetics.
Psychopharmacology
January 1, 1964
D. E. Rosenberg, Harris Isbell, E. J. Miner et al.
60 citations
No Summary
Psychopharmacology
January 22, 2022
Steven A. Barker
59 citations
The route, form, and dose of a drug critically shape its pharmacology and therapeutic use. This review focuses on the psychedelic N,N-dimethyltryptamine (DMT), examining positive and negative aspects of various formulations and routes of administration, including ayahuasca teas, oral "pharmahuasca," intravenous and intramuscular injections, inhalation, insufflation, and high-dose, low-dose, and micro-dose effects. It considers possible oral alternatives that would not require a monoamine oxidase inhibitor. The review also addresses current in vivo and in vitro research findings and the possibility that these findings may reveal a role for endogenous DMT in normal brain function.
Psychopharmacology
September 13, 2021
Friederike Holze, Toya V Caluori, Patrick Vizeli et al.
57 citations
LSD dose-dependently increased subjective, physiologic, and adverse effects in healthy subjects. Positive subjective effects (good drug effect) were more pronounced than negative ones (bad drug effect), with maximal ratings of >50% good drug effects reached in 37%, 91%, 96%, and 91% of administrations at 25, 50, 100, and 200 µg, respectively, versus 0%, 9%, 27%, and 31% for bad drug effects. Physiologic effects were moderate: no systolic blood pressure exceeded 180 mmHg, peak heart rate >100 beats/min occurred in up to 25% of subjects at the highest dose, and peak body temperature >38°C in up to 34%. Kidney and liver function remained unaltered. Six subjects reported transient flashbacks. Single-dose LSD is safe regarding acute psychological and physical harm in healthy subjects in a controlled research setting.
Psychopharmacology
April 1, 2009
Lisa E Baker, John J Panos, Bryan A Killinger et al.
57 citations
Salvinorin A, the active compound in the hallucinogenic plant Salvia divinorum, produces its effects through kappa opioid receptors. In experiments with male Sprague-Dawley rats trained to discriminate between two different kappa opioid agonists (U69,593 or U50,488), salvinorin A and two synthetic derivatives of salvinorin B fully substituted for the training drugs, indicating they produce similar internal sensations. Additional rats trained to discriminate salvinorin A also recognized the other kappa agonists. These results confirm that salvinorin A's discriminative stimulus effects are mediated by kappa receptors, supporting the potential use of salvinorin A analogs as therapeutic agents for conditions like drug dependence and mood disorders.
Psychopharmacology
July 23, 2020
Nige Netzband, Simon Ruffell, Sabriya Linton et al.
56 citations
Ayahuasca, a psychoactive brew containing DMT and MAOIs, is traditionally used ceremonially in the Amazon and increasingly by tourists seeking healing or spiritual growth. In a mixed-design study, 24 participants who ingested ayahuasca showed significant increases in agreeableness and reductions in neuroticism compared to a control group, with changes sustained at a 6-month follow-up; trait openness also increased at follow-up. Greater perceived mystical experience was linked to larger reductions in neuroticism. These results suggest a positive mediating effect of ayahuasca on personality, supporting potential therapeutic uses for serotonergic psychedelics.
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 psychedelic that activates 5-HT2A receptors, disrupted early perceptual and higher-order cognitive processing in healthy volunteers but left pre-attentive cognition intact. In a double-blind, placebo-controlled crossover trial, 20 participants (10 men, 10 women) received 0.26 mg/kg of psilocybin orally. The drug produced robust psychedelic effects and psychotic-like symptoms, decreased the amplitude of the P300 event-related potential (a marker of attentive processing) and the N100 (an early perceptual marker), but did not affect mismatch negativity (MMN), a measure of pre-attentive processing. The disruption of P300 correlated with the intensity of the psychedelic state, which depended on psilocin serum levels. These findings suggest that 5-HT2A receptors play a role in altered information processing in psychosis and schizophrenia, particularly at early perceptual and higher-order cognitive levels.
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.