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.
Annals of the New York Academy of Sciences
November 20, 2023
Katarina Jerotic, Peter Vuust, Morten L. Kringelbach
19 citations
Music and psychedelics have been intertwined throughout human history, from early shamanic rituals to modern psychedelic-assisted therapy. This review examines their interplay, describing how both engage the brain's functional hierarchy for music perception and its psychedelic-induced manipulation. It explores music's role in Western psychedelic therapy and indigenous rituals, focusing on ayahuasca and the Santo Daime Church. The work also considers music's potential to induce altered states of consciousness without psychedelics and the development of psychedelic music. The authors provide an overview of several perspectives on this interaction, a topic of growing interest given increasing excitement about psychedelic interventions' therapeutic efficacy.
Annals of the New York Academy of Sciences
August 26, 2022
C. Martial, O. Gosseries, H. Cassol et al.
17 citations
This commentary criticizes a recent paper by Parnia and colleagues that proposed guidelines for studying death and near-death experiences. The authors argue that the original paper contains omissions and knowledge gaps, including incorrect neurological claims about brain death and misunderstandings about consciousness terminology. While the commentators agree that research on near-death experiences needs a framework, they contend that the Parnia paper is misleading and, despite its intentions, actually impedes scientific understanding of near-death experiences and the neural mechanisms of the dying brain.
Annals of the New York Academy of Sciences
August 1, 2005
Ronald I. Herning
17 citations
People who use MDMA (ecstasy) show distinct brain changes compared to those who use only marijuana or no drugs. In a study of eight MDMA users, eight users of both MDMA and marijuana, fifteen marijuana-only users, and seventeen non-user controls, electroencephalography (EEG) recordings revealed that MDMA users had significantly higher absolute delta wave power at central electrode sites, a pattern not seen in the other groups. Marijuana-only users showed increases in alpha-2 power. Blood flow velocity in the middle cerebral arteries, measured by transcranial Doppler, was higher in MDMA users regardless of marijuana use. These brain changes, similar to those seen in chronic disorders, suggest MDMA may cause long-term neurological harm, though more research is needed.
Annals of the New York Academy of Sciences
October 31, 1996
J P O'Callaghan, T S Rogers, L E Rodman et al.
14 citations
High doses of ibogaine, a psychoactive alkaloid, damage brain regions beyond the cerebellum in rats, with effects depending on sex and dosage. Single doses caused dose-related increases in GFAP, a marker of brain cell injury, across multiple brain areas in both sexes. Repeated doses led to large GFAP increases (up to 200% of control) in the hippocampus, olfactory bulbs, brain stem, and striatum of female rats but not males. In the hippocampus of chronically treated females, other structural proteins also increased, suggesting a sprouting response to damage. The findings indicate that ibogaine's neurotoxic effects are not limited to the cerebellum and vary by sex and dosing schedule.
Annals of the New York Academy of Sciences
June 21, 2022
R. Evrard, E. Pratte, Th. Rabeyron
13 citations
A critique argues that a recent proposal to relabel near-death experiences (NDEs) as “recalled experience of death” and to consider only those with objective danger as “authentic” is not well supported by data. Instead, NDEs form a continuum of varied conscious experiences arising from the separation of processes normally combined in mental activity. The claimed core phenomenology of NDEs faces multiple criticisms, and closeness to actual death is not a decisive feature. The authors’ reliance on Raymond Moody’s model creates a biased division that cannot serve as a basis for consensus.
Annals of the New York Academy of Sciences
May 1, 1998
Emmanuel S Onaivi, Syed F Ali, Amitabha Chakrabarti
13 citations
Ibogaine, a substance with potential antiaddiction effects against alcohol, psychostimulants, and opiates, was studied in mice and cell cultures to explore its mechanism. In mice, acute ibogaine doses reduced aversion to open arms in a plus-maze test, while subacute administration caused fluctuating aversive and antiaversive behavior over 14 days. Ibogaine reversed withdrawal aversions in mice abruptly withdrawn from cocaine. In PC 12 cells, cocaine disrupted signal transduction by altering protein kinase C isoform expression and activity and calcium levels. The findings suggest ibogaine's antiaddictive property may involve modifying central nervous system neurotransmission related to anxiety, but whether PKC signaling is important remains unknown.
Annals of the New York Academy of Sciences
May 1, 1998
Zbigniew Binienda, Michael A Beaudoin, Brett T Thorn et al.
13 citations
Ibogaine, a psychoactive alkaloid with antiaddictive properties, can cause neurotoxicity. In anesthetized rats, a single 50 mg/kg dose of ibogaine produced an immediate decrease in heart rate and reduced EEG power across delta, theta, alpha, and beta frequency bands during the first 30 minutes, with recovery within 15 minutes. In the caudate nucleus, dopamine levels fell while dopamine turnover increased; serotonin levels rose in the frontal cortex. These physiological changes likely stem from ibogaine's interactions with multiple neurotransmitter systems.