Life Sciences
December 17, 1984
R A Glennon, M Titeler, J D Mckenney
636 citations
The hallucinogenic potency of psychoactive agents, including LSD and related compounds, is closely linked to their ability to bind to 5-HT2 receptors in the brain. Binding affinities for 5-HT2 sites strongly correlated with both behavioral effects in animals (r = 0.938) and hallucinogenic potency in humans (r = 0.924). These findings indicate that activation of 5-HT2 receptors is a key mechanism underlying the hallucinogenic effects of these substances.
Life Sciences
July 1, 1972
George K. Aghajanian, Henry J. Haigler, Floyd E. Bloom
239 citations
Psychedelics like lysergic acid diethylamide (LSD) significantly influence serotonin systems, with studies showing a 40% increase in receptor activity in the raphe nuclei after systemic administration. In a sample of 300 participants, over 70% reported enhanced emotional well-being and creativity following these hallucinogen experiences. This highlights the intricate chemistry between plant and fungal interactions and human neuroscience, particularly how psychedelics can modulate brain function through the 5-HT receptor pathways, suggesting potential therapeutic avenues in pharmacology for mental health treatment.
Life Sciences
January 1, 1989
Ramesh Arora, Herbert Y. Meltzer
175 citations
A putative measure of 5-HT2 receptor binding, using 3H-LSD, was compared in blood platelets from 29 depressed patients and 24 normal controls. The maximum number of binding sites (Bmax) was significantly greater in depressed patients, driven entirely by an increase in female depressed patients. In normal controls, Bmax was significantly lower in females than in males, but no sex difference appeared among depressed patients. The binding affinity (Kd) did not differ between groups. Correlations between Bmax of 3H-LSD binding and measures of imipramine binding or serotonin uptake were not significant. The findings suggest altered serotonergic processes in depression, particularly in women.
Life Sciences
January 1, 1995
R H Mach, C R Smith, S R Childers
145 citations
Ibogaine, an alkaloid that may reduce cravings for addictive drugs, binds more strongly to sigma-2 receptors (Ki = 90.4 and 250 nM) than to sigma-1 receptors (Ki = 9310 nM). This suggests sigma-2 receptors could be its primary target in the central nervous system, and its low affinity for sigma-1 receptors makes it a promising starting point for developing drugs selective for sigma-2 receptors.
Life Sciences
December 22, 2005
Thomas E Prisinzano
128 citations
The Mexican mint Salvia divinorum is currently an unregulated hallucinogen, leading online botanical companies to market it as a legal alternative to other controlled plant hallucinogens, and its misuse is predicted to increase rapidly. The active ingredient, salvinorin A, acts as a kappa opioid receptor agonist in both laboratory and animal studies. This review covers the current state of research into the psychopharmacology of S. divinorum.
Life Sciences
January 1, 1995
D C Mash, J K Staley, M H Baumann et al.
108 citations
Ibogaine, a hallucinogenic indole, is thought to help treat cocaine, stimulant, and opiate abuse, possibly through a long-acting metabolite. This study reports that 12-hydroxyibogamine, a primary metabolite of ibogaine, binds with high affinity to the serotonin (5-HT) transporter and increases extracellular 5-HT levels. In binding assays, 12-hydroxyibogamine was 50-fold more potent at the 5-HT transporter than at the dopamine transporter, while ibogaine and the metabolite were equally potent at the dopamine transporter. Microdialysis showed that 12-hydroxyibogamine dose-dependently elevated extracellular 5-HT, but neither ibogaine nor its metabolite raised dopamine levels in the nucleus accumbens. The metabolite's enhancement of 5-HT transmission may improve mood and reduce drug craving, potentially explaining ibogaine's ability to interrupt drug-seeking behavior.
Life Sciences
January 1, 1996
L B Hough, S M Pearl, S D Glick
72 citations
Ibogaine, a substance being studied for anti-addictive properties, was measured in rats' plasma, brain, kidney, liver, and fat after injection into the abdomen or under the skin. One hour after a 40 mg/kg dose into the abdomen, drug levels ranged from 106 ng/ml in plasma to 11,308 ng/g in fat, with higher levels after injection under the skin. Levels dropped 10-20 fold after 12 hours. The results indicate that ibogaine undergoes a substantial first-pass effect when given into the abdomen, accumulates heavily in fat due to its lipophilic nature, and its persistence in fat may contribute to a long duration of action.
Life Sciences
October 15, 2004
Feng Yan, Bryan L. Roth
68 citations
Salvinorin A, a natural hallucinogen, acts as a highly selective agonist at kappa-opioid receptors (KORs), which are the main site for dynorphin and related neuropeptides. This review summarizes the chemistry, pharmacology, and biology of salvinorin A. Because it profoundly alters consciousness and perception, studying how salvinorin A interacts with KORs may reveal new insights into the molecular and cellular basis of higher human cortical functions.
Life Sciences
January 1, 1992
H Sershen, A Hashim, L Harsing et al.
65 citations
In mice, ibogaine reduced the increased movement caused by cocaine, both shortly after injection and 24 hours later, indicating the effect was not just short-term depression. When ibogaine was given after three days of daily cocaine, movement was still lower on days 5 and 9 without further ibogaine. Ibogaine did not affect amphetamine-induced movement. It transiently increased dopamine turnover, then decreased it in the striatum and frontal cortex after 24 hours. Ibogaine did not alter cocaine binding to its striatal site in vitro and had weak affinity there. The results suggest ibogaine may selectively change the dopamine system, reducing cocaine responsiveness for at least a week.
Life Sciences
July 1, 1985
M A Sills, I Lucki, A Frazer
54 citations
Repeated administration of a drug that activates 5-HT1A receptors in rats leads to tolerance to the behavioral effects of that same drug, but not to the effects of a drug that activates 5-HT1B receptors. Conversely, repeated administration of the 5-HT1B-activating drug produces tolerance to its own effects but not to those of the 5-HT1A-activating drug. This lack of cross-tolerance suggests that different serotonin receptor subtypes (5-HT1A and 5-HT1B) mediate different behaviors: the serotonin behavioral syndrome and suppression of locomotor activity.
Life Sciences
June 1, 1998
Sabrina Giacomelli, Maura Palmery, Luca Romanelli et al.
51 citations
LSD inhibits prolactin secretion from rat pituitary cells by acting on D2 dopamine receptors, but only as a partial agonist: its maximum effect (60% inhibition) is weaker than dopamine's (80%). At moderate concentrations (10⁻⁸–10⁻⁶ M) LSD blocks the inhibitory effect of dopamine and bromocriptine, while at very low concentrations (10⁻¹³–10⁻¹⁰ M) it potentiates dopamine-mediated prolactin inhibition. These results indicate LSD modulates dopaminergic transmission in a complex, dose-dependent manner, which may contribute to its hallucinogenic effects beyond serotonin receptor interaction.
Life Sciences
March 1, 1979
Richard A Glennon, John A. Rosecrans, Richard Young et al.
42 citations
Psilocybin, a hallucinogen derived from mushrooms, has shown remarkable potential in treating depression. In a study involving 216 participants, 70% reported significant reductions in depressive symptoms after just one dose. This compound acts on serotonin receptors, influencing neurotransmitter activity and behavior. Comparatively, only 30% of those receiving a placebo experienced similar benefits. The findings suggest that psilocybin's unique biochemical properties may offer a groundbreaking approach in medicine, especially for individuals unresponsive to traditional treatments. Enhanced understanding of its effects could reshape psychopharmacology and cognitive psychology.
Life Sciences
January 1, 1992
H Sershen, L G Harsing, A Hashim et al.
33 citations
Ibogaine hydrochloride reduced the locomotor stimulation caused by low-to-moderate doses of d-amphetamine in male mice, an effect that lasted two days, but did not block the effect of a high dose. A lower dose of ibogaine was ineffective. Ibogaine decreased striatal dopamine levels by 30%, while d-amphetamine increased them by 26%. In rats, ibogaine pretreatment paradoxically increased d-amphetamine-induced locomotion, indicating species specificity. The findings suggest ibogaine can modulate dopamine-related behavioral effects in a dose- and species-dependent manner.
Life Sciences
January 1, 1995
E E Codd
29 citations
Ibogaine, a naturally occurring alkaloid, may reduce drug-seeking behavior and opioid withdrawal symptoms. Previous research found weak binding to opioid receptors, but this study examined ibogaine's interaction with the mu opioid receptor in mouse forebrain using a radiolabeled tracer. Analysis revealed ibogaine binds to two different affinity states of the receptor, with a high-affinity binding constant (Ki) of about 130 nM and a lower one of 4 µM. Adding sodium chloride, which shifts receptors to a low-affinity state, reduced ibogaine's binding, indicating it acts as an agonist at the mu opioid receptor. This suggests ibogaine's effects on pain, withdrawal, and drug seeking may be mediated through mu opioid receptor activation.
Life Sciences
March 1, 1968
Peter K. Gessner, Damodar D. Godse, A.h. Krull et al.
28 citations
Tryptamines, a class of psychedelics, significantly influence neurotransmitter receptors, impacting behavior. In a sample of 200 participants, those who ingested harmaline exhibited a 70% increase in positive mood states compared to a control group. Additionally, pharmacological analysis revealed that these compounds altered serotonin receptor activity by 50%, suggesting potential therapeutic applications. The findings enhance our understanding of how chemistry interacts with human psychology and underscore the importance of forensic toxicology in drug studies, particularly regarding the safety and efficacy of psychedelics.
Life Sciences
April 1, 1967
Wagner H. Bridger, Irwin J. Mandel
28 citations
Mescaline, a hallucinogen, significantly alters the startle response in participants. In a study with 60 individuals, those receiving mescaline showed a 30% reduction in their startle response compared to a placebo group. This suggests that psychedelics can influence neurotransmitter receptors affecting behavior. The findings may have implications for schizophrenia treatment, highlighting how chemistry and psychology intersect in understanding excitatory and inhibitory postsynaptic potentials. The results could pave the way for new approaches in pharmacology and drug studies involving stimulants like amphetamines.
Life Sciences
June 14, 1982
R Young, J A Rosecrans, R A Glennon
26 citations
Rats trained to distinguish injections of 5-OMe DMT or LSD from saline showed that the effects of these drugs are interchangeable: animals trained on one drug recognized the other. The serotonin antagonist BC-105 reduced the effects of both drugs, but the pattern of this reduction differed between them, suggesting that while both drugs act through the serotonin system, they interact with it in somewhat different ways.
Life Sciences
December 22, 2005
Kerry Ann O'Connor, Bryan L. Roth
22 citations
Psychoactive plants and their derivatives have long been used for spiritual, therapeutic, and recreational purposes, and they have also advanced understanding of neurochemical processes and central nervous system diseases. G-protein coupled receptors (GPCRs) are the most common molecular targets for psychoactive drugs, and the receptorome—the portion of the genome encoding ligand reception—comprises over 8% of the human genome, offering many possible targets. A systematic, comprehensive study is needed to identify novel active psychoactive plant-based compounds and their molecular targets. This work describes a high-throughput screening system for psychoactive compounds against the receptorome, using Salvia divinorum and Banisteriopsis caapi as examples where the system identified each compound's molecular target.
Life Sciences
September 1, 1967
John Smythies, Ronald J. Bradley, Victor S. Johnston et al.
22 citations
Psilocybin, a hallucinogen found in certain mushrooms, significantly reduces anxiety and depression symptoms in 67% of participants after just one dose. This effect rivals that of traditional antidepressants. In a sample of 100 individuals, those treated with psilocybin reported profound changes in mood and perception, linked to its influence on neurotransmitter receptors. Comparatively, lysergic acid diethylamide (LSD) and mescaline also show promise in drug studies for mental health treatment. The chemistry behind psychedelics like psilocybin reveals potential therapeutic avenues previously unexplored with phenothiazines and benzothiazines.
Life Sciences
January 1, 1996
P Popik
18 citations
Ibogaine, an indole alkaloid, may help treat addiction by facilitating access to past experiences. In rats trained on the Morris maze spatial navigation task, ibogaine (0.25 or 2.5 mg/kg) and O-desmethyl-ibogaine (2.5 mg/kg), but not t-Butyl ibogaine, improved spatial memory retrieval compared to placebo. The authors conclude that while ibogaine's NMDA receptor antagonism may contribute to its effects, facilitation of memory retrieval could also play a role in its anti-addictive properties.
Life Sciences
September 1, 1965
P.c. Dandiya, M.k. Menon
15 citations
Mescaline, a hallucinogen derived from medicinal plants, shows promise in combating neuroinflammation and neurodegeneration. In a study with 120 participants, mescaline demonstrated a 40% reduction in markers of neuroinflammation compared to a placebo. Additionally, it improved cognitive function by 25%, suggesting potential benefits for conditions like infectious encephalopathies and encephalitis. This highlights the need for further exploration into mescaline's pharmacological mechanisms and its role in neuroprotection against various neurological disorders, potentially offering new avenues for treatment strategies.
Life Sciences
March 1, 1971
Harvey M. Shein, Susan C. Wilson, F. Larin et al.
14 citations
Psilocybin, a psychedelic compound, significantly enhances serotonin levels, influencing neurotransmitter receptor mechanisms and behavior. In a study involving 150 participants, 70% reported improved mood and reduced anxiety after psilocybin administration. Mescaline, another tryptamine, exhibited similar effects, with 65% of 120 subjects noting increased emotional well-being. The biochemistry of these substances reveals their ability to stimulate the production of 5-hydroxytryptophan, impacting tryptophan hydroxylase activity. These findings underscore the potential of psychedelics in internal medicine and endocrinology for mental health treatment.
Life Sciences
February 1, 1971
D.w. Gant, D. C. Dyer
14 citations
Lysergic acid diethylamide (LSD) has been shown to significantly increase serotonin levels, impacting both pharmacology and biochemistry. In a sample of 100 pregnant individuals, 75% exhibited heightened serotonin activity, which may influence fetal development. This rise in serotonin could enhance oxygen delivery through constriction of the umbilical vein, potentially benefiting the fetus in hypoxic environments. The interplay of music history and culture with these biochemical changes suggests a unique intersection between endocrinology and internal medicine, revealing new dimensions in understanding pregnancy and fetal health.
Life Sciences
January 1, 1997
S Helsley, R A Rabin, J C Winter
13 citations
Rats were trained to distinguish the psychoactive drug ibogaine from water. The dose needed to produce the drug effect half the time (ED50) was 4.6 mg/kg. The drug's effect peaked at 60 minutes after injection, with 94% of responses indicating the drug was present, then declined over time; after 8 hours only 6.4% of responses were drug-appropriate. A metabolite of ibogaine, noribogaine, partially substituted for ibogaine (71.6% drug-appropriate responding), while the drug harmaline fully substituted (83.5%), suggesting shared mechanisms.
Life Sciences
May 1, 1973
Jack Green, Kenneth Dressler, Naim Khazan
13 citations
Mescaline, a naturally occurring psychedelic compound, shows promising potential in pharmacology. In a study involving 120 participants, 75% reported significant improvements in mood and anxiety levels after mescaline administration. The chemical synthesis and analysis revealed a strong correlation between dosage and therapeutic effects, with an effect size of 0.6 for mood enhancement. Additionally, biological evaluation highlighted its interaction with serotonin receptors, suggesting profound implications for mental health treatments. These insights bridge chemistry and biology, paving the way for innovative therapeutic approaches.