Abstract MDMA given at recreational doses (range tested 50 to 150 mg) to healthy volunteers, produced mydriasis and marked increases in systolic and diastolic blood pressure, heart rate, and pupillary diameter. MDMA induced changes on oral temperature. The time course of this observation was biphasic, as a slight decrease at 1 h and a slight increase at 2 and 4 h were observed. MDMA induced a...
Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term...
18-MC, a novel iboga alkaloid congener, is being developed as a potential treatment for multiple forms of drug abuse. Like ibogaine (40 mg/kg), 18-MC (40 mg/kg) decreases the intravenous self-administration of morphine and cocaine and the oral self-administration of ethanol and nicotine in rats; unlike ibogaine, 18-MC does not affect responding for a nondrug reinforcer (water). Both ibogaine...
Abstract MDMA (3,4‐methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a “chemical stressor.” It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a...
Ibogaine (IBO) is a plant-derived alkaloid that is being evaluated as a possible medication for substance use disorders. When administered peripherally to monkeys and humans, IBO is rapidly converted to an o-demethylated metabolite, 12-hydroxyibogamine (NORIBO). We have found in rats that peak blood levels of NORIBO can exceed those of the parent compound, and NORIBO persists in the bloodstream...
The psychoactive indole alkaloid, ibogaine (IBO), has been investigated for over a decade concerning its reported anti-addictive properties for opioids as well as psychomotor stimulants. The mechanism for the anti-addictive action of IBO is still unclear. IBO interactions with opioid, NMDA, nicotinic, adrenergic, and serotonergic receptor sites have been suggested. The involvement of the...
Ibogaine, one of several alkaloids found in the root bark of the African shrub Tabernanthe iboga, has been claimed to be effective in treating multiple forms of drug abuse. Problems associated with side effects of ibogaine have spawned a search for more effective and safer structural derivatives. 18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, appears to have substantial...
There has been considerable interest in the potential of N-methyl-D-aspartate (NMDA) receptor antagonists in the treatment of a diverse group of neurological disorders including cerebral ischemia and neurodegeneration. The amino acids L-glutamate and L-aspartate have been shown to possibly mediate excitatory synaptic transmission in the central nervous system (CNS) via selective excitatory...
The potential for deriving new psychotherapeutic medications from natural sources has led to renewed interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous...
Ibogaine, an alkaloid extracted from Tabemanthe iboga, is being studied as a potential long-acting treatment for oploid and stimulant abuse as well as for alcoholism and smoking. Studies in this laboratory have used animal models to characterize ibogaine's interactions with drugs of abuse, and to investigate the mechanisms responsible. Ibogaine, as well as its metabolite, noribogaine, can...
ABSTRACT: The acute behavioral effects of methylenedioxymethamphetamine (MDMA) and dexfenfluramine (d‐FEN) were assessed in six rhesus monkeys using performance in the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB); three additional animals served as controls for neurochemical endpoints. The OTB consists of five food‐reinforced tasks designed to model aspects of...
Although the alkaloid ibogaine is a potent hallucinogenic agent some indications suggest that it may be useful for the treatment of opioid and cocaine addiction. The neurochemical mechanism(s) underlying ibogaine effects remain unclear. In the present study we investigated the interaction of ibogaine with the phencyclidine (PCP) site located in the ionophore of the N-methyl-d-aspartate (NMDA)...
Ibogaine may have antiaddiction potential against alcohol, psychostimulant and opiate abuse, but its mechanism of action is unclear. Ibogaine, however, has been demonstrated in numerous studies to have effects in multiple central nervous system (CNS) neurotransmitters systems. We are using in vitro and in vivo systems to study the effects of cocaine and whether these effects can be blocked by...
Ibogaine (IBO) is a psychoactive indole alkaloid that has antiaddictive properties. However, treatment with IBO may lead to neurotoxicity, since IBO and its metabolites interact persistently with many neurotransmitter systems. Here, we recorded cortical electroencephalogram (EEG) signals from rats anesthetized with isoflurane. The heart rate (HR) was monitored via electrocardiogram (EKG)...
Ibogaine (IBO) is a naturally-occurring indole compound that is being evaluated as a potential medication for substance use disorders. Although the precise mechanism of IBO action is unclear, recent in vitro data show this drug displays properties similar to the noncompetitive N-methyl-d-aspartate (NMDA) antagonist MK-801. The purpose of the present work was to compare In Vivo neurobiological...
New technologies utilized for monitoring brain function can be more sensitive in the assessment of desired or undesired pharmacological effects than can clinical examination. Nonetheless, careful case-by-case analysis is required to determine to what extent a change detected with a sensitive imaging modality will have clinical significance. Whereas in some instances the technology may suggest a...
Acute administration of high doses of ibogaine (IBG) to the male rat results in degeneration of Purkinje cells and reactive gliosis in the cerebellar vermis. We examined whether acute and chronic administration of IBG to male and female rats results in gliosis as determined by quantification of the astroglial intermediate filament protein, glial fibrillary acidic protein (GFAP). After acute...
To analyze the mechanisms of PCP abuse, we investigated the changes in PCP-induced motivational properties and neuronal functions in animals. First, we determined that PCP-induced withdrawal syndrome may, in part, be produced by 5-HTergic neuronal systems. Second, using rats treated with subacute PCP, we established that subacute PCP may produce behavioral changes (stereotyped behaviors and...
Frontal-subcortical circuits provide a comprehensive framework for understanding the anatomy, biochemistry, and pharmacology of behavior. The three principal behaviorally relevant circuits originate in the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex, respectively. Circuit-specific marker behaviors associated with each circuit are executive dysfunction...
The cytotoxic effects of amphetamine derivatives were studied by immunocytochemistry to identify the cellular compartments affected by these drugs, to obtain morphologic evidence of neuronal degeneration, and to assess the potential for regeneration. The substituted amphetamines, MDA, MDMA, PCA, and fenfluramine, all release serotonin and cause acute depletion of 5-HT from most axon terminals...
In summary, the data from both neurochemical and neuroanatomical studies demonstrate widespread and long-lasting degeneration of serotonin neurons in brain without any major or consistent effects on catecholamine neurons following in vivo administration of MDMA in both rats and rhesus monkeys. A detailed examination of the parameters involved in the neurotoxic and neurodegenerative effects of...
The data presented herein appear to strongly implicate the brain 5HT2 receptor as the site-of-action of the hallucinogenic PIAs and LSD. If so, this discovery represents a major step in understanding the molecular pharmacology of hallucinogenic drugs. Using radioactive hallucinogenic drugs, detailed properties of brain 5HT2 receptors indicating the interaction of 5HT2 receptors with GTP-binding...
Clinical observation suggests that cannabis is implicated in some types of psychiatric disturbance. A record of admissions to two urban and four rural hospitals in Jamaica is examined along with details of individual cases. One-third of male admissions to the psychiatric hospital have used cannabis. Of 74 males admitted to another psychiatric service over a 12-month period, 29 had used...
Late in the 1950s, Axelrod became interested in the distribution, excretion, metabolization and rate of "biotransformation" of lysergic acid diethylamide (LSD) by the body. In this first of several articles on the narcotic drug, he detailed the subcellular processes involved in the transformation of LSD, determined the order of concentrations of the drug in various tissues, determined that it...