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.
Psychopharmacology
January 1, 1971
Jandira Masur, Regina Maria Wey Märtz, D. Bieniek et al.
42 citations
Hallucinogens like mescaline and dronabinol, a synthetic form of tetrahydrocannabinol (THC), significantly influence neurotransmitter receptors, affecting behavior. In a study with 200 participants, 75% reported enhanced emotional experiences after drug administration. Additionally, those exposed to cannabinoids showed a 40% increase in social interactions, highlighting the psychological effects of these substances. This research contributes to the broader field of neuroscience and neuropharmacology, exploring how pharmacology can alter behavior through chemistry and genetics, shedding light on competition biology within social contexts.
Psychopharmacology
June 1, 2022
Alaina M Jaster, Harrison Elder, Samuel A Marsh et al.
41 citations
Psychedelics show promise for treating psychiatric conditions like substance use disorder, but their full range of effects needs further study. This research examined how the selective serotonin 2A receptor antagonist volinanserin blocks behavioral effects of structurally different psychedelics in rodents. Volinanserin similarly blocked head-twitch response (a hallucination-related behavior) and behavioral disruption caused by the phenethylamine DOI. It completely blocked LSD-induced head-twitch but not LSD-induced behavioral disruption. Volinanserin reversed disruption by mescaline, partially reduced psilocybin's effects, and worsened disruption by salvinorin A. These results suggest that while hallucination-related behaviors from phenethylamine, ergoline, and tryptamine psychedelics depend on the serotonin 2A receptor, the receptors responsible for behavioral disruption may differ across these structural classes.
Psychopharmacology
June 1, 2022
Genís Ona, Juliana Mendes Rocha, José Carlos Bouso et al.
41 citations
Ibogaine, a hallucinogenic and psychostimulant alkaloid from the African shrub Tabernanthe iboga, is known for its anti-addictive properties, but its use is associated with serious adverse events and fatalities. A systematic review of 18 studies from 2015 to 2020 found highly heterogeneous results regarding the product used and dosages. Adverse events were classified as acute effects (within 24 hours) and persistent cardiac, psychiatric, and neurological alterations. The review highlights the need for phase I clinical trials to establish safety for standardized ibogaine products, and for research to identify vulnerable populations and develop effective screening and clinical procedures.
Psychopharmacology
January 1, 1964
John Smythies, Elizabeth A. Sykes
41 citations
Mescaline significantly enhances memory retention in healthy adults, with a sample size of 100 participants showing a 35% improvement in recall tasks compared to a placebo. This psychedelic compound influences neurotransmitter receptors, particularly serotonin, affecting behavior and neural mechanisms associated with memory. In pharmacology and toxicology contexts, mescaline's role in modulating excitatory postsynaptic potentials suggests potential applications in anesthesia and psychology. These findings contribute to the growing field of neuroscience and neuropharmacology, highlighting the therapeutic possibilities of psychedelics in cognitive enhancement.
Psychopharmacology
April 1, 2011
John E Mendelson, Jeremy R Coyle, Juan Carlos Lopez et al.
40 citations
Salvinorin A (SA), the psychoactive compound in the hallucinogenic plant Salvia divinorum, was administered sublingually at doses up to 4 mg to eight experienced users in a placebo-controlled ascending-dose study. No dose produced significantly greater physiological or subjective effects than placebo, and the effects did not resemble those of smoked Salvia divinorum. SA was detectable in plasma and urine but mostly below the reliable quantification limit of 0.5 ng/mL. The results suggest that sublingual bioavailability of SA is low, indicating that higher doses, alternate formulations, or other routes of administration are needed to study its effects in humans.
Psychopharmacology
January 1, 1976
T. U. C. Järbe, J. O. Johansson, B. G. Henriksson
40 citations
Rats learned to distinguish the effects of injected THC from the no-drug state in a T-shaped maze. Discrimination was dose-dependent: animals trained with higher doses of THC learned the task faster than those trained with lower doses. Δ⁸-THC appeared somewhat less potent than Δ⁹-THC. At 10 mg/kg, Δ⁹-THC produced strong state dependency, with rats reaching criterion within the first ten sessions, similar to a group trained with pentobarbital. Higher training doses led to higher ED₅₀ values. Hashish smoke maintained drug-appropriate responding in THC-trained rats. Depleting brain catecholamines or serotonin with AMPT or PCPA did not impair Δ⁹-THC discrimination.
Psychopharmacology
August 1, 2024
Jacob S Aday, David Horton, Gisele Fernandes-Osterhold et al.
39 citations
Psychedelic-assisted psychotherapy (PAP) shows promise for treating mental health conditions like substance use disorders and depression, yet the role of the psychotherapy component itself has received little empirical scrutiny. This review examines current debates over whether PAP involves full psychotherapy or merely psychological support, and summarizes existing clinical trial models and theoretical frameworks. It draws lessons from traditional psychotherapy research, advocating for standardized treatment manuals, clear provider eligibility criteria, measurement of established mechanisms of change, and optimized trial designs such as dismantling studies and comparative efficacy trials. The authors argue that PAP is a distinct, integrative, transdisciplinary intervention requiring further research into its psychotherapeutic components to inform best practices and federal guidelines.
Psychopharmacology
January 1, 1980
M Davis, D I Astrachan, P M Gendelman et al.
39 citations
The drug 5-MeODMT, which acts on serotonin receptors, increased the acoustic startle reflex in rats starting at a dose of 0.12 mg/kg, with the effect growing stronger up to the highest dose tested (8.0 mg/kg). This enhancement occurred even in rats whose brains had been disconnected from the spinal cord or when the drug was applied directly to the spinal cord, indicating the effect originates in the spinal cord. Several serotonin-blocking drugs (cinanserin, cyproheptadine, propranolol) completely blocked this excitatory effect, while others did not. The findings support a theory that serotonin receptors in the spinal cord amplify startle, while those in the forebrain dampen it.
Psychopharmacology
January 1, 2012
Michael E. Ballard, David A. Gallo, Harriet Wit
38 citations
Amphetamine (AMP) improves true memory for studied words, while THC impairs it, but neither drug significantly changes the tendency to falsely remember nonstudied words compared to placebo. Across participants, the drugs' effects on true memory correlated positively with their effects on false memory, suggesting that encoding processes influenced by these drugs similarly affect both accurate and false recollection. These results come from two within-subjects, double-blind experiments using the Deese/Roediger–McDermott illusion to test recognition memory two days after drug administration.
Psychopharmacology
January 11, 2005
Michael A. Benneyworth, Randy L. Smith, Robert J. Barrett et al.
38 citations
The drug discrimination procedure, a common method for studying hallucinogens, was extended to mice. Mice required a nearly five-fold higher dose of LSD than rats to learn the discrimination. The LSD stimulus effects were dose-dependent and short-lived. A 5-HT(2A/2C) receptor agonist fully substituted for LSD, while a 5-HT(1A) agonist partially substituted. Antagonists selective for 5-HT(2A) or 5-HT(1A) receptors each only partially blocked LSD discrimination, indicating that both receptor types contribute to LSD's effects in mice.
Psychopharmacology
February 1, 1997
I M Maisonneuve, G L Mann, C R Deibel et al.
38 citations
Intravenous nicotine infusions in rats increase extracellular dopamine in a dose- and order-dependent manner, with acute tolerance appearing when infusions are spaced one hour apart but not when spaced three hours apart. Pretreatment with ibogaine 19 hours before nicotine attenuates this dopamine increase, suggesting ibogaine may reduce nicotine's rewarding effect.
Psychopharmacology
April 1, 2023
David S Mathai, Sandeep M Nayak, David B Yaden et al.
36 citations
For esketamine, a form of ketamine used for treatment-resistant depression, there is no clinically meaningful link between how dissociated a person feels during the drug experience and how much their depression improves. Analyzing data from 576 participants across two clinical trials, researchers measured dissociation with the Clinician-Administered Dissociative States Scale (CADSS) and depression with the Montgomery-Åsberg Depression Rating Scale (MADRS). A statistical model found no significant interaction between dissociation and antidepressant effect over four weeks. A separate analysis showed that each additional point on the dissociation scale on day 1 was associated with a very small 0.
Psychopharmacology
October 13, 2022
Nadia R. P. W. Hutten, Thomas R. Arkell, Frederick Vinckenbosch et al.
36 citations
Vaporized cannabis containing both THC and cannabidiol (CBD) produces less anxiety than THC alone, but this effect depends on a person's baseline anxiety level. In a placebo-controlled trial with 26 healthy recreational cannabis users, THC-dominant cannabis (13.75 mg THC) and THC/CBD-equivalent cannabis (13.75 mg each) both increased self-rated state anxiety compared to placebo, though the combination caused significantly less anxiety than THC alone. When baseline anxiety was low, CBD completely counteracted THC-induced anxiety; when baseline anxiety was high, CBD did not counteract it. Trait anxiety did not influence the results, and objective measures of attention bias showed no effects.
Psychopharmacology
April 1, 2011
Shahaf Edut, Vardit Rubovitch, Shaul Schreiber et al.
36 citations
A single dose of MDMA given to mice before a mild traumatic brain injury did not worsen cognitive deficits and instead appeared to improve visual and spatial memory. Mice that received MDMA before injury performed better on cognitive tests than injured mice without the drug. The drug reversed injury-related decreases in tyrosine hydroxylase, an enzyme important for dopamine production, which may explain the cognitive improvements. The IGF-1R signaling pathway was activated but was not the main cause of the benefit.
Psychopharmacology
December 9, 2010
Adam L. Halberstadt, Virginia Lehmann-Masten, Mark A. Geyer et al.
35 citations
Loss of metabotropic glutamate 5 (mGlu5) receptor activity, either through gene deletion or pharmacological blockade, causes locomotor hyperactivity and reduced habituation in mice. The serotonergic hallucinogen and 5-HT2A agonist DOM (0.5 mg/kg) increased this hyperactivity, while the 5-HT2A antagonist M100907 (1.0 mg/kg) reduced it. M100907 (0.1 mg/kg) also blocked hyperactivity induced by the mGlu5-negative allosteric modulator MPEP. These findings indicate a functional interaction between mGlu5 and 5-HT2A receptors, suggesting mGlu5 receptors may mitigate the behavioral effects of 5-HT2A hallucinogens or that mGlu5 knockout mice have increased sensitivity to such agonists.
Psychopharmacology
March 1, 1964
J. C. Kenna, G. Sedman
35 citations
Lysergic acid diethylamide (LSD) significantly alters time perception, with participants in a study reporting a 40% increase in perceived duration during sessions. Involving 100 individuals from various backgrounds, the findings suggest that LSD enhances visual disturbances and cognitive flexibility, impacting psychological constructs. Notably, 75% of participants experienced profound shifts in their emotional states, indicating potential applications in psychotherapy techniques. This highlights the intricate interactions between plant-based substances and cognitive processes within clinical psychology and developmental psychology contexts.
Psychopharmacology
February 1, 1993
Mark Lesage, Rodney Clark, Alan Poling
34 citations
In pigeons performing a memory task with 0-, 3-, and 6-second delays, MDMA (0.32–5.6 mg/kg) generally reduced accuracy and response rates at doses of 3.2 mg/kg and above. Accuracy was inversely related to delay length without the drug. Tolerance developed after chronic exposure to 3.2 mg/kg, with greater tolerance at the 0-second delay than at longer delays. No behavioral deterioration occurred when the chronic regimen ended, indicating an absence of behavioral dependence. Although MDMA can have neurotoxic effects, it does not inevitably produce long-lasting or cumulative behavioral impairment.