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
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
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
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
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
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
January 1, 1996
E D French, K Dillon, S F Ali
12 citations
Ibogaine, a plant-derived alkaloid, acutely excites dopamine neurons in the ventral tegmental area (VTA) of anesthetized rats, but this effect is not long-lasting. Pretreatment with ibogaine 6-8 hours or 19 hours before testing did not alter the spontaneous firing of VTA dopamine neurons or their response to morphine or cocaine. Because ibogaine's excitatory effect on these neurons is transient and does not persistently change how dopamine neurons respond to these drugs, other mechanisms must explain its proposed antiaddictive properties.
Life sciences
December 6, 1982
J A Clemens, M E Roush
8 citations
In male rats, the serotonin agonist 5-MeODMT did not alter basal prolactin levels at doses from 1.0 to 20.0 mg/kg. However, pretreatment with 5-MeODMT reduced prolactin release stimulated by agents that rely on serotonergic neurotransmission, specifically L-5-hydroxytryptophan (5-HTP) and morphine. These results suggest that 5-MeODMT acts as a presynaptic serotonin autoreceptor stimulant rather than a post-synaptic serotonin agonist in the neuronal systems controlling prolactin release.
Life sciences
February 1, 1982
R A Glennon, R Young, F Benington et al.
8 citations
Rats trained to distinguish the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a drug discrimination task were tested with three related compounds: the 4-methoxy, 4-methylthio, and 5-methylthio derivatives of DMT. All three derivatives produced effects similar to the original drug. The relative potency of the compounds, from most to least potent, was 5-OMe DMT, followed by 5-SMe DMT, then 4-OMe DMT, and finally 4-SMe DMT.
Life sciences
November 17, 2000
C Acuña-castillo, C Scorza, M Reyes-Parada et al.
3 citations
ALEPH-2, a phenylisopropylamine derivative with claimed anxiolytic and hallucinogenic effects, acts as a partial agonist on the 5-HT2A receptor with potency similar to serotonin, but as a full agonist on the 5-HT2C receptor, where it is about 15-fold less potent than serotonin. The antagonist ritanserin blocks responses to both serotonin and ALEPH-2 equally, though the 5-HT2A receptor is more sensitive to ritanserin than the 5-HT2C receptor.
Life sciences
March 19, 1984
A A Larson
3 citations
In cats, a single injection of LSD increased the dorsal root potential evoked by stimulating the nucleus raphe magnus, while a single injection of 5-MeODMT decreased it. The dose and time course of these electrophysiological changes matched the drugs' known behavioral effects. After four daily LSD injections, complete tolerance developed to LSD's potentiating effect, but the same pretreatment with 5-MeODMT did not alter its acute inhibitory effect. These results parallel the development of behavioral tolerance to LSD and 5-MeODMT, suggesting this system may serve as an electrophysiological model for studying these drugs.