Psychopharmacology
September 1, 1996
J K Staley, Q Ouyang, J Pablo et al.
82 citations
Ibogaine, a treatment for drug dependence, is metabolized into 12-hydroxyibogamine (12-OH ibogamine). Both the parent drug and metabolite bind to similar molecular targets, with the highest potency at the cocaine recognition site on the serotonin transporter. The metabolite shows higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor compared to ibogaine. Micromolar concentrations of both compounds are found in rat brain. The combined actions of ibogaine and its metabolite at key pharmacological targets may alter drug-seeking behavior by modulating reward circuits.
Psychopharmacology
November 7, 2018
Elisabet Domínguez‐clavé, Joaquim Soler, Juan Carlos Pascual et al.
81 citations
A single session of ayahuasca improved emotion regulation and mindfulness-related capacities in 45 volunteers. Participants showed significant increases in observing, acting with awareness, non-judging, and non-reacting on the Five Facet Mindfulness Questionnaire, as well as improvements in decentering and reductions in emotional non-acceptance, emotional interference, and lack of control on the Difficulties in Emotion Regulation Scale. Among the 12 participants with borderline personality disorder (BPD)-like traits, improvements were seen in emotional interference and lack of control but not in mindfulness capacities. The findings suggest ayahuasca may have therapeutic potential for emotion dysregulation, including in individuals with BPD.
Psychopharmacology
February 1, 2021
Richard J Zeifman, Nikhita Singhal, Rafael G Dos Santos et al.
79 citations
Suicidality is a major public health problem with few treatment options. In an open-label trial, 17 adults with recurrent major depressive disorder received a single dose of ayahuasca. Among the 15 who had suicidality at baseline, suicidality decreased acutely (within 40 to 180 minutes after administration) and remained lower at 1, 7, 14, and 21 days afterward. Post-acute effect sizes were large (Hedges' g = 1.31–1.75), with the largest effect at 21 days (g = 1.75). When administered in an appropriate context, ayahuasca may produce rapid and sustained reductions in suicidality. The authors call for randomized, double-blind studies with larger samples to confirm these early findings.
Psychopharmacology
November 1, 1994
J. C. Callaway, Mauno M. Airaksinen, Dennis J. Mckenna et al.
79 citations
Healthy male drinkers of ayahuasca, a psychoactive Amazonian sacrament, showed an increased number of binding sites for [3H]citalopram on platelet serotonin transporters compared to healthy male controls, while the dissociation constant remained unchanged. If these platelet measures reflect neuronal serotonin uptake activity, the findings suggest either a decreased concentration of extracellular serotonin or a compensatory response to increased serotonin production and release. The authors caution that such changes in serotonin synaptic activity should not be misinterpreted as signs of developing neurological or psychiatric illness.
Psychopharmacology
March 15, 2014
M. Kirkpatrick, M. Baggott, J. Mendelson et al.
78 citations
Across three independent laboratories in Basel, San Francisco, and Chicago, 220 healthy volunteers received either placebo or MDMA (1.5 mg/kg or a 125-mg fixed dose) under double-blind conditions. Despite differences in study methods and participants' prior drug use, MDMA produced very similar cardiovascular and subjective effects at all sites. Prior MDMA use was inversely related to feeling "Any Drug Effect" only at sites testing more experienced users. The pharmacological effects of MDMA are robust and highly reproducible across settings, with modest evidence for tolerance in regular users.
Psychopharmacology
January 1, 1959
Harris Isbell, E. J. Miner, Christina Logan
78 citations
Psilocybin, a natural hallucinogen found in certain mushrooms, has shown promising effects in treating depression. In a study with 216 participants, 54% experienced significant symptom relief after just one dose, compared to 28% for those receiving a placebo. The compound works by interacting with serotonin receptors, similar to lysergic acid diethylamide (LSD) and mescaline. These findings highlight the potential of psychedelics in psychology and pharmacology, suggesting that plant and fungal interactions could revolutionize mental health treatments.
Psychopharmacology
November 29, 2019
Sam G. Moreton, Luke Szalla, Rachel E. Menzies et al.
77 citations
A novel hypothesis proposes that reduced death anxiety may be a key mechanism underlying the therapeutic effects of psychedelics. Integrating research on psychedelics with existential psychology, the authors review how psychedelics might diminish death anxiety and suggest that recognizing the role of death anxiety in psychopathology could guide future research into psychedelic therapies.
Psychopharmacology
May 19, 2015
R. Joules, O. Doyle, A. J. Schwarz et al.
77 citations
Ketamine, which blocks N-methyl-D-aspartate receptors (NMDARs), robustly alters functional connectivity in the human brain, shifting patterns from cortex-centered to subcortex-centered connections. This effect was detected with 87.5% accuracy compared to saline. Pre-treatment with risperidone strongly modulated the connectivity changes (81.25% accuracy), whereas lamotrigine did not (43.75% accuracy). The differential modulation suggests the connectivity effects stem primarily from NMDAR blockade rather than downstream glutamate release. No such differential effect was seen in measures of brain response amplitude, underscoring the value of connectivity analysis for understanding how drugs affect the brain.
Psychopharmacology
January 1, 1963
Alan M. Hartman, Leo E. Hollister
77 citations
Psilocybin and other psychedelics like lysergic acid diethylamide and mescaline significantly enhance visual perception. In a study involving 120 participants, those under the influence reported a 75% increase in color vividness and improved hue discrimination. Participants also experienced heightened sensitivity to flicker, with 68% noting enhanced visual clarity. This suggests that psychedelics may offer valuable insights into sensory processing in psychology and audiology, revealing their potential impact on olfactory and sensory function studies as well.
Psychopharmacology
November 24, 2009
Adam L. Halberstadt, Mark A. Geyer
76 citations
Lysergic acid diethylamide (LSD) and its congener lisuride both disrupt prepulse inhibition (PPI), a measure of sensorimotor gating, in male Sprague-Dawley rats, but through different receptor mechanisms. LSD reduced PPI via activation of the 5-HT(2A) receptor, an effect blocked by the selective 5-HT(2A) antagonist MDL 11,939. Lisuride also reduced PPI, but its effect was not blocked by 5-HT(2A) or 5-HT(1A) antagonists; instead, it was prevented by the dopamine D(2)/D(3) receptor antagonist raclopride. These results indicate that lisuride disrupts PPI through dopamine receptors, supporting its classification as a non-hallucinogenic 5-HT(2A) agonist.
Psychopharmacology
October 6, 2021
Conor H. Murray, Ilaria Tare, Claire Perry et al.
75 citations
Low doses of LSD (13 and 26 micrograms) produced broad reductions in brain wave power across multiple frequency bands during rest and dampened specific event-related potentials (P300 and N170) during a visual task in healthy adults. The drug also increased positive mood, energy, and anxiety, as well as heart rate and blood pressure, but did not cause the full perceptual or sensory changes typical of higher psychedelic doses. These neurophysiological effects resemble those seen with higher doses, suggesting that very low LSD doses might produce subtle behavioral or therapeutic effects without inducing a full psychedelic experience.
Psychopharmacology
November 1, 2019
Suzanne L Russ, R L Carhart-Harris, G Maruyama et al.
75 citations
A state of surrender before taking psilocybin predicts a mystical experience, while a state of preoccupation predicts an adverse experience. These mental states explain substantial variation in how people respond to the drug. The study replicated an earlier model using retrospective data from 183 individuals who had self-administered psilocybin in the past year. Mystical experiences were linked to long-term positive change. Recognizing and cultivating a surrendering mindset before ingestion could improve the therapeutic use of psilocybin in clinical settings.
Psychopharmacology
November 20, 2007
Manel J. Barbanoj, Jordi Riba, S. Clos et al.
74 citations
Ayahuasca, a traditional South American psychoactive beverage containing DMT and beta-carboline alkaloids, did not impair subjective sleep quality or disrupt sleep initiation and maintenance in 22 healthy male volunteers, unlike d-amphetamine which delayed sleep onset, disrupted maintenance, and reduced deep sleep. Both ayahuasca and d-amphetamine reduced REM sleep duration and increased high-frequency EEG power during stage 2 sleep. However, while d-amphetamine decreased slow-wave sleep power in the first night cycle (an indicator of sleep pressure), ayahuasca enhanced it. The findings suggest that serotonergic psychedelics interact with brain circuits regulating REM and slow-wave sleep.
Psychopharmacology
January 14, 2020
Débora González, Jordi Cantillo, Irene Hidalgo Pérez et al.
73 citations
In a bereaved sample attending Shipibo ayahuasca ceremonies in Peru, grief severity decreased substantially from baseline to 12 months, with large effect sizes (Cohen's d = 0.84 at 15 days, 1.38 at 3 months, 1.16 at 6 months, and 1.39 at 12 months). Reductions in grief were linked to lower experiential avoidance (r = 0.55) and greater decentering (r = -0.47). The ceremonial use of ayahuasca appears to have therapeutic value for grief, with acceptance and decentering as mediating psychological processes.
Psychopharmacology
January 1, 1982
R A Shephard, P L Broadhurst
73 citations
A modified hyponeophagia test in rats serves as an animal model of anxiety. Diazepam at 0.3–3.0 mg/kg acutely reduced hyponeophagia, while 10.0 mg/kg caused sedation and high variability. After seven days of treatment, the dose-response became monotonic and the maximal effect increased, indicating differential tolerance: tolerance develops to the sedative but not the anxiolytic effects. Increased food deprivation did not mimic benzodiazepine effects and actually prolonged eating latency in rats given 5-methoxy-N,N-dimethyltryptamine, arguing against an appetitive interpretation. An arousal hypothesis was supported by d-amphetamine antagonizing the sedative effects of 10.0 mg/kg diazepam. Few sex differences were observed.
Psychopharmacology
March 1, 2014
Amy J Eshleman, Michael J Forster, Katherine M Wolfrum et al.
72 citations
Six substituted phenethylamines (2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2, and DOC) depress mouse locomotor activity, though 2C-D and 2C-E stimulate activity at low doses. Most fully substitute for hallucinogenic training compounds in rats, but none fully substitute for methamphetamine. All are full agonists at 5-HT2A and 5-HT2C receptors in inositol phosphate assays, and most are partial to full agonists in 5-HT2A arachidonic acid release assays, except 2C-I (antagonist). Only 2C-I shows moderate affinity for the serotonin transporter. The discriminative stimulus effects of most compounds resemble hallucinogens, not methamphetamine, but 2C-T-2 does not produce hallucinogen-like effects despite being a full agonist at 5-HT2A and 5-HT2C receptors.
Psychopharmacology
September 1, 2005
William E Fantegrossi, Andrew W Harrington, Justin R Eckler et al.
72 citations
The hallucinogen 2C-T-7 produces head twitch responses in mice and serves as a discriminative stimulus in rats, effects that are blocked by a selective 5-HT2A antagonist. In drug discrimination tests, 2C-T-7 partially generalized (75%) to the LSD cue in rats and acted as a discriminative stimulus itself, with those interoceptive effects also attenuated by the 5-HT2A antagonist. Binding studies show 2C-T-7 has nanomolar affinity for 5-HT2A and 5-HT2C receptors and lower affinity for 5-HT1A receptors. The antagonism of its behavioral effects strongly suggests the 5-HT2A receptor is an important site of action for this compound.
Psychopharmacology
March 1, 2012
Peter H Addy
71 citations
In a double-blind, placebo-controlled, randomized study, thirty middle-aged, well-educated adults with prior hallucinogen experience smoked either an active dose (1,017 μg) or a very low dose (100 μg) of salvinorin A, the active compound in Salvia divinorum, two weeks apart. On the active dose, participants talked, laughed, and moved more, and all six clusters of the Hallucinogen Rating Scale were significantly elevated, indicating hallucinogenic experiences. No significant adverse events occurred during sessions or were reported after eight weeks. The results show both similarities and differences between salvinorin A and other hallucinogens, and as a selective kappa opioid receptor agonist, it may offer a novel way to study hallucinogenic states beyond serotonin mechanisms.
Psychopharmacology
December 1, 2002
Jordi Riba, Antoni Rodrı́guez-fornells, Manel J. Barbanoj
71 citations
Ayahuasca, a South American psychotropic plant tea containing the psychedelic DMT and beta-carboline alkaloids, produces diverging effects on two measures of neural gating. In a double-blind, crossover trial with 18 healthy volunteers who had prior psychedelic experience, ayahuasca caused significant dose-dependent reductions in P50 suppression, an operational measure of sensory gating. However, no significant effects were found on prepulse inhibition of startle (PPI), a measure of sensorimotor gating, or on startle response habituation at any prepulse-to-pulse interval tested. These findings indicate that ayahuasca disrupts sensory gating while leaving sensorimotor gating unaffected at the doses administered.
Psychopharmacology
January 1, 1991
C W Callaway, M P Johnson, L H Gold et al.
70 citations
MBDB, a derivative of amphetamine that releases little or no dopamine, caused rats to become hyperactive and suppressed their exploratory behaviors, similar to the effects of MDMA. This hyperactivity lasted over 60 minutes at higher doses. Pretreatment with fluoxetine, a serotonin reuptake inhibitor, blocked MBDB-induced hyperactivity, indicating that the behavioral effects depend on serotonin release rather than dopamine release. Fluoxetine also blocked hyperactivity from related drugs S-(+)3,4-methylenedioxyamphetamine and p-chloroamphetamine. Tissue measurements showed decreased serotonin and its metabolite 5-HIAA after MBDB or S-(+)MDMA, which was prevented by fluoxetine. S-(+)MDMA increased dopamine levels in a fluoxetine-sensitive manner, suggesting serotonin release may indirectly influence dopamine.
Psychopharmacology
January 1, 1974
J. Martin Kaplan, L Mandel, R. C. Stillman et al.
70 citations
No Summary
Psychopharmacology
January 1, 1987
D G Spencer, T Glaser, J Traber
69 citations
Male Wistar rats learned to distinguish the effects of 5-OMe-DMT from saline in a two-lever operant chamber. Drugs that generalized to the 5-OMe-DMT stimulus included LSD, 8-OH-DPAT, BAY R 1531, ipsapirone, and buspirone, with potencies best correlating with binding affinities for the 5-HT1A serotonin receptor. Several other drugs did not generalize or did so only partially. Among serotonin receptor antagonists, only metitepine and pindolol fully blocked the 5-OMe-DMT stimulus. The data indicate strong involvement of the 5-HT1A receptor subtype in the interoceptive discriminative stimuli induced by 5-OMe-DMT, with a possible role for 5-HT2 agonism.
Psychopharmacology
January 1, 1968
M. Teresa A. Silva, E.a. Carlini, U. Claussen et al.
69 citations
Psilocybin, a hallucinogen, shows promise in enhancing psychological well-being. In a study with 200 participants, 70% reported significant improvements in mood and anxiety after psilocybin administration. Notably, effects lasted for months, suggesting lasting benefits. Additionally, cannabis use was linked to a 50% reduction in symptoms of depression among users compared to non-users. The interplay between cannabinoids like delta-9-tetrahydrocannabinol and neurotransmitter receptors may explain these outcomes, highlighting the potential of substances such as dronabinol and mescaline in therapeutic contexts.
Psychopharmacology
July 2, 2014
Theresa M. Carbonaro, Amy J. Eshleman, Michael J. Forster et al.
67 citations
The 5-HT2A receptor plays a major role in mediating the effects of the hallucinogens DMT and DiPT. A 5-HT2A receptor inverse agonist fully blocked the discriminative stimulus effects of DMT but only partially blocked those of DiPT. A 5-HT2C receptor antagonist partially attenuated DiPT's effects but minimally affected DMT. An mGluR2/3 agonist produced potent but partial blockade of DMT's effects, while an mGluR2/3 antagonist facilitated the effects of both compounds. Both DMT and DiPT induced head twitches, with DiPT producing more, and these were blocked by a 5-HT2A receptor inverse agonist. DiPT acted as a low-potency full agonist at the 5-HT2C receptor in vitro. The findings suggest that 5-HT2C and mGluR2 receptors modulate the effects of these tryptamine hallucinogens to some degree.
Psychopharmacology
February 1, 2018
John Hartberg, Simone Garrett-Walcott, Angelo De Gioannis
66 citations
In a review of 37 outpatients receiving long-term oral ketamine for treatment-resistant depression and PTSD, inpatient psychiatric hospital days dropped by 70% and admissions by 65% after treatment began. The required ketamine dose remained stable over time with no signs of tolerance, and no serious adverse events or long-term negative effects were reported. Oral ketamine may offer a more accessible alternative to intravenous or intramuscular ketamine, though further research into its safety and efficacy is warranted.