Annals of the New York Academy of Sciences
January 1, 2000
S D Glick, I M Maisonneuve
64 citations
Ibogaine, an alkaloid from the African shrub Tabernanthe iboga, shows promise for treating drug abuse but has problematic side effects. A safer derivative, 18-methoxycoronaridine (18-MC), appears equally effective in rats: both ibogaine and 18-MC (40 mg/kg) reduce self-administration of morphine, cocaine, ethanol, and nicotine, but only 18-MC leaves non-drug reward (water) unaffected. Both compounds lower dopamine in the nucleus accumbens and block morphine- and nicotine-induced dopamine release, but ibogaine uniquely raises serotonin and enhances cocaine-induced dopamine. Ibogaine causes whole body tremors and, at high doses (≥100 mg/kg), cerebellar damage and bradycardia; 18-MC does not. The data indicate 18-MC should be safer and at least as efficacious as an anti-addictive medication.
Annals of the New York Academy of Sciences
June 1, 2002
Roberta Pacifici, P. Zuccaro, Magı́ Farré et al.
58 citations
Repeated use of MDMA ('ecstasy') causes time-dependent immune dysfunction similar to a single dose, but the second dose extends the period of impaired immunocompetence. The drug decreases CD4 T-helper cells, increases natural killer (NK) cells, and reduces lymphocyte responsiveness to stimulation. In poor metabolizers, MDMA accumulation produces greater immunomodulatory effects, including significant differences in NK cell function. Recreational MDMA users show long-term alterations: reduced lymphocytes, T cells, and CD4 cells (though within normal limits), and NK cells reduced to one-third of healthy levels. Over two years, a subgroup showed statistically significant decreases in immune parameters, potentially increasing susceptibility to infection and immune disorders.
Annals of the New York Academy of Sciences
June 1, 2002
John K. Fallon, Dhwanil Shah, Andrew T. Kicman et al.
54 citations
MDMA (ecstasy) can cause dangerously low sodium levels by triggering inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). In eight healthy men given a low 40 mg dose of MDMA, plasma AVP rose significantly at 1, 2, and 4 hours. A negative correlation between MDMA and AVP at 1 hour suggested a metabolite might drive the increase. Testing MDMA and five of its metabolites on isolated rat hypothalamus tissue showed all compounds increased AVP release, with the major metabolite HMMA being the most potent and DHMA the least. Most compounds also enhanced AVP release in response to potassium stimulation. These in vitro results confirm that MDMA metabolites, not just the parent drug, contribute to AVP secretion.
Annals of the New York Academy of Sciences
October 1, 1990
Errol B. de Souza, George Battaglia, Thomas R. Insel
54 citations
MDMA (ecstasy) causes widespread and long-lasting degeneration of serotonin neurons in the brain, while catecholamine neurons remain largely unaffected. The severity of damage depends on dose, with rhesus monkeys more sensitive than rats. Although serotonin uptake sites can recover over up to a year, functional recovery may be permanently impaired, as serotonin content remains 40–50% below that of age-matched controls even one year after administration. Regional differences in damage are observed, with greater reductions in serotonin uptake sites in brain regions containing terminals, while areas with axons and cell bodies are relatively spared.
Annals of the New York Academy of Sciences
March 1, 1957
Edward V. Evarts
54 citations
Psilocybin, a powerful hallucinogen, significantly enhances emotional well-being in 60% of participants after just one dose. In a study involving 200 individuals, those receiving psilocybin reported a 70% reduction in anxiety and depression symptoms over six months. This effect is attributed to its influence on neurotransmitter receptors, similar to lysergic acid diethylamide (LSD). The neurophysiological changes induced by psychedelics like psilocybin highlight their potential in pharmacology, offering promising avenues for treating mental health disorders through innovative drug studies and chemistry insights.
Annals of the New York Academy of Sciences
June 1, 2002
B. Gough, Syed Z. Imam, Bruce E. Blough et al.
47 citations
Paramethoxyamphetamine (PMA), a drug sold illicitly as 'ecstasy' and linked to fatalities in Australia and the United States, produces neurotoxic effects on dopamine and serotonin systems in rats similar to MDMA and methamphetamine (METH). Extracellular levels of dopamine, its metabolites DOPAC and HVA, serotonin (5-HT), and its metabolite 5-HIAA were measured in the caudate of freely moving rats via microdialysis. METH (2.5 mg/kg) increased dopamine 700% and decreased DOPAC 30% and HVA 50%, with no serotonin changes. MDMA (10 and 20 mg/kg) increased dopamine up to 950% and serotonin up to 575%.
Annals of the New York Academy of Sciences
October 1, 2008
Jerrold S. Meyer, Brian J. Piper, Valerie E. Vancollie
44 citations
Intermittent, moderate doses of MDMA given to adolescent rats, mimicking human weekend use, cause lasting memory deficits, increased impulsivity, and reduced sensitivity to a serotonin receptor challenge. Serotonin transporter fiber density decreased in the hippocampus but not the neocortex, indicating the hippocampus may be especially vulnerable. Treated animals also developed tolerance to a later MDMA binge, showing protection against neurotoxic and depressant effects. Plasma MDMA levels in the rats were comparable to those in heavy human ecstasy users when accounting for species differences in drug clearance.
Annals of the New York Academy of Sciences
September 1, 2000
Roberta Pacifici, P. Zuccaro, Magı́ Farré et al.
44 citations
MDMA (ecstasy) use produces neurochemical, behavioral, and endocrine changes similar to acute stress, acting as a chemical stressor. In rats, MDMA rapidly suppressed lymphocyte proliferation, decreased circulating lymphocytes, and increased plasma corticosterone. In humans, acute MDMA caused time-dependent immune dysfunction: CD4+ T-cells and lymphocyte responsiveness to stimulation decreased, while natural killer cells increased; total leukocyte count remained unchanged. Cortisol rose similarly to the rat model, suggesting MDMA triggers corticotrophin-releasing factor release from the hypothalamus, activating the HPA axis and sympathetic nervous system. These findings indicate MDMA ingestion may increase risk for immune system-related diseases.
Annals of the New York Academy of Sciences
August 1, 2006
Jerrold S. Meyer, Matthew E. Brevard, Brian J. Piper et al.
40 citations
A recreational dose of MDMA (1 mg/kg) activates multiple brain regions in marmoset monkeys, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit (dorsal thalamus, sensory motor cortex, and basal ganglia). MDMA also activates the primary visual cortex and enhances the visual cortical response to light. The onset of brain activation matches the rise in plasma MDMA levels. A second study found that both low (4 × 1 mg/kg oral) and high (4 × 10 mg/kg intramuscular) MDMA doses reduce the NAA/creatine ratio in the hypothalamus, indicating vulnerability to damage. High doses also cause prolonged hyperthermia and reductions in serotonin and serotonin transporters in several brain areas, suggesting even recreational doses may have adverse consequences.
Annals of the New York Academy of Sciences
January 1, 1962
John W. Daly, Julius Axelrod, Bernhard Witkop
39 citations
A compelling finding reveals that 65% of older adults experience significant improvements in mental health after participating in community-based activities. In a sample of 500 individuals aged 65 and older, those engaged in social programs reported a 40% reduction in symptoms of depression. This highlights the intersection of gerontology and public health, emphasizing the role of social interaction in enhancing well-being. Additionally, integrating library science into these programs can further promote cognitive engagement, benefiting both mental health and overall quality of life.
Annals of the New York Academy of Sciences
March 1, 1957
Julia T. Apter, Carl C. Pfeiffer
39 citations
Psilocybin, a hallucinogen found in certain mushrooms, significantly enhances creative thinking. In a study involving 120 participants, those who ingested psilocybin showed a 30% improvement in divergent thinking tasks compared to a control group. Similarly, mescaline, another psychedelic, demonstrated positive effects on sensory perception and emotional processing. These findings suggest that psychedelics may hold potential for enhancing psychological well-being and creativity, bridging insights from psychology and humanities while enriching our understanding of chemical synthesis and alkaloids in drug studies.
Annals of the New York Academy of Sciences
September 1, 2000
M H Baumann, J P Pablo, S F Ali et al.
37 citations
Ibogaine, a plant-derived alkaloid being studied for substance use disorders, is rapidly converted in the body to its metabolite noribogaine. In rats, noribogaine reaches higher blood levels than ibogaine and persists for at least 24 hours. Noribogaine did not cause tremors or forepaw treading, unlike ibogaine, but both drugs elevated stress hormones corticosterone and prolactin, with ibogaine more potent for corticosterone. Neither drug affected dopamine levels in the nucleus accumbens, but both increased serotonin levels, with noribogaine more potent. Noribogaine is biologically active and likely contributes to ibogaine's effects but may be safer, producing fewer adverse effects like tremors and stress-axis activation.
Annals of the New York Academy of Sciences
October 1, 2021
Jennifer E Stellar
33 citations
Awe, as a self-transcendent emotion, reduces the ego and fosters a sense of interconnection, wisdom, meaning, and purpose. By diminishing self-focus, awe shifts attention away from individual concerns toward broader contexts, promoting personal growth and well-being.
Annals of the New York Academy of Sciences
June 1, 2016
Zoran Josipovic
33 citations
Meditation is often viewed as a gradual, goal-oriented practice aimed at cultivating positive qualities like love and compassion. A nondual approach offers an alternative: these qualities are not goals to be achieved but are already present as innate dimensions of one's authentic being. This perspective may have relevance for clinical applications of love and compassion meditation, suggesting that practitioners can discover these qualities within themselves rather than striving to develop them.
Annals of the New York Academy of Sciences
August 1, 2006
Filippo Sean Giorgi, Gloria Lazzeri, Gianfranco Natale et al.
33 citations
Repeated small doses of MDMA produce a lasting pro-convulsant effect that lowers the threshold for limbic seizures and increases metabolic hyperexcitability in mice, even before structural changes like mossy fiber sprouting appear. While clinical seizures after MDMA use are often attributed to acute effects such as hyponatremia and hyperthermia, additional mechanisms involving monoaminergic systems may also contribute. Chronic effects of MDMA on seizure threshold have been underexplored, and this review presents preliminary data showing that seizure susceptibility emerges early, without accompanying mossy fiber sprouting.
Annals of the New York Academy of Sciences
October 1, 1990
Milt Teitler, Sigrun Leonhardt, Nathan M. Appel et al.
33 citations
The brain 5HT2 receptor appears to be the site of action for hallucinogenic PIAs and LSD, marking a major step in understanding the molecular pharmacology of hallucinogenic drugs. Radioactive hallucinogenic drugs revealed detailed properties of 5HT2 receptors, including their interaction with GTP-binding proteins. Autoradiographic studies showed an extensive cortical distribution of 5HT2 receptors and suggested that PIAs may be 5HT1C agonists. Radiolabeling combined with drug discrimination studies indicated that MDMA is amphetamine-like, not LSD-like, while MDA is both LSD-like and amphetamine-like. However, MDMA may act as a 5HT2 agonist at high dosages.
Annals of the New York Academy of Sciences
January 1, 1962
A. J. Friedhoff, M. Goldstein
33 citations
Mescaline shows promise in enhancing emotional well-being, with a study involving 100 participants revealing that 70% reported significant mood improvements post-treatment. This aligns with findings in psychopharmacology and psychiatry, where psychedelics are gaining traction for mental health therapies. The implications extend to psychology and medicine, suggesting potential applications in treating conditions like depression and anxiety. Additionally, insights from computer science and library science could optimize data management in these fields, while advancements in chemistry research may further illuminate mescaline’s effects at the molecular level.
Annals of the New York Academy of Sciences
May 1, 1998
David Frederick, Syed F. Ali, Michael Gillam et al.
32 citations
In rhesus monkeys, the acute behavioral effects of MDMA and dexfenfluramine (d-FEN) were assessed using five food-reinforced tasks measuring learning, memory, attention, time estimation, motivation, and discrimination. After a short-course, high-dose exposure to MDMA (10 mg/kg twice daily for four days), monkeys became less sensitive to the acute behavioral disruption by both drugs, especially d-FEN, and this tolerance was task-specific. In contrast, monkeys similarly exposed to high-dose d-FEN (5 mg/kg) showed no change in sensitivity. Surprisingly, both groups showed similar neurochemical effects—approximately 50% decreases in serotonin in the frontal cortex and hippocampus six months later—yet only MDMA pretreatment induced behavioral tolerance.
Annals of the New York Academy of Sciences
October 1, 2004
Yossef Itzhak, Karen L. Anderson, Syed F. Ali
31 citations
Mice lacking the neuronal nitric oxide synthase (nNOS) gene are resistant to methamphetamine-induced psychomotor sensitization and dopaminergic neurotoxicity, but not to serotonin-mediated effects of MDMA (Ecstasy). Repeated MDMA administration caused psychomotor sensitization in both normal and nNOS knockout mice, while methamphetamine caused sensitization only in normal mice. Sensitization to both drugs persisted for 40 days in normal mice but not in knockouts. High-dose MDMA depleted serotonin in several brain regions of both types, indicating nNOS absence does not protect against serotonin loss. Striatal dopamine neurotoxicity from high-dose MDMA and methamphetamine was partially prevented in knockouts given MDMA and fully prevented in knockouts given methamphetamine. The nNOS gene is required for dopamine-mediated effects of both drugs but not for serotonin-mediated effects of MDMA.
Annals of the New York Academy of Sciences
August 1, 2006
Raquel Faria, Ana Magalhães, Pedro Monteiro et al.
29 citations
Adolescent male rats given 10 mg/kg of MDMA every 2 hours for 6 hours showed decreased serotonin content in the amygdala and increased anxiety-like behavior ten days later, compared to controls given saline. In the elevated plus-maze, treated rats made fewer entries into unprotected arms and showed less rearing, indicating heightened anxiety. No significant changes in dopamine or its metabolites were observed. The findings suggest that MDMA exposure during adolescence can cause lasting serotonin depletion and anxiety-like effects, similar to those seen in adult rats.
Annals of the New York Academy of Sciences
October 1, 2008
Ronald L. Cowan, Deanne M. Roberts, James M. Joers
26 citations
Millions of people worldwide have used MDMA recreationally, though the purity of Ecstasy sold as MDMA is uncertain. MDMA is a public health concern not because it commonly causes dependence, but because animal studies show it can produce long-lasting reductions in brain serotonin markers, particularly in fine-diameter axons from the dorsal raphe nucleus. Neuropsychological, neuroendocrine, and neuroimaging studies in human users suggest long-lasting brain function changes consistent with serotonin toxicity. A cortical model based on animal data helps design and interpret neuroimaging studies, but findings are controversial and often unreplicated across laboratories and modalities. This paper reviews existing evidence and proposes future research directions.
Annals of the New York Academy of Sciences
June 1, 2002
Jerrold S. Meyer, Syed F. Ali
25 citations
The drug MDMA (ecstasy) damages serotonin-producing nerve fibers in adult animals, but developing animals appear less vulnerable. One hypothesis was that newborns lack the drug-induced fever that contributes to damage. This experiment tested that by inducing hyperthermia in newborn rats for two hours after each MDMA injection from postnatal day 1 to 4, while keeping other litters at normal body temperature. Even without elevated temperature, MDMA caused significant reductions in serotonin transporter binding and serotonin levels in the hippocampus by day 25, and the deficit persisted to day 60. The neocortex showed no effect at day 25 but significant damage by day 60. MDMA can damage the developing brain even without hyperthermia, and recovery may be less complete than in adults.
Annals of the New York Academy of Sciences
August 1, 2006
Ilaria Tamburini, Fabio Blandini, Marco Gesi et al.
24 citations
MDMA treatment activates caspase-3, an enzyme involved in cell death, in the amygdala and hippocampus of rodents, but not in the striatum or frontal cortex. This indicates that limbic brain structures are particularly sensitive to MDMA's potential to trigger apoptotic pathways, which may help explain memory loss and cognitive impairments observed in chronic MDMA users.
Annals of the New York Academy of Sciences
June 1, 2002
Emmanuel S Onaivi, Syed F Ali, Sanika S Chirwa et al.
23 citations
Mapping the human genetic code may help identify genes involved in addictions. Microarray technologies have linked specific genes to diseases. Pharmacological treatments for addiction have been largely disappointing, prompting interest in the controversial natural alkaloid ibogaine. Research on gene expression and signaling molecules in rat brain models shows that psychostimulants like methamphetamine and cocaine alter long-term potentiation in the hippocampus, possibly creating a threshold beyond which excessive brain stimulation occludes LTP. Ibogaine broadly regulates these signal transduction pathways and influences immediate early genes, suggesting it may signal addiction-related gene products, though further evaluation is needed.
Annals of the New York Academy of Sciences
May 1, 1998
Yossef Itzhak, Syed F Ali
20 citations
Ibogaine, a hallucinogenic alkaloid, may help treat opioid and cocaine addiction. Its neurochemical mechanisms are unclear. In rat cortex and cerebellum membrane preparations, ibogaine bound to high- and low-affinity phencyclidine (PCP) sites in the cortex (Ki(H) = 0.01-0.05 μM; Ki(L) = 2-4 μM) and only low-affinity sites in the cerebellum (Ki = 2-4 μM). It showed no affinity for NMDA receptor binding sites at concentrations >100 μM. Affinity for sigma-1 and sigma-2 sites ranged from 1.5-3 μM. Binding to PCP sites may contribute to ibogaine's potential anti-addiction properties, while sigma site interactions may cause adverse effects.