Science
August 19, 2010
Nanxin Li, Boyoung Lee, Rongjian Liu et al.
2,875 citations
Ketamine, a drug that blocks NMDA receptors, rapidly activates the mTOR pathway in the prefrontal cortex of rats, increasing synaptic signaling proteins and the number and function of new spine synapses. Blocking mTOR signaling prevented ketamine from inducing synaptogenesis and behavioral antidepressant-like responses in depression models. These effects reverse the synaptic deficits caused by stress and may explain ketamine's fast antidepressant action in treatment-resistant depressed patients, which contrasts with the weeks or months needed for standard medications.
Science
August 16, 1968
George K. Aghajanian, Warren E. Foote, Michael Sheard
406 citations
Injections of d-lysergic acid diethylamide (LSD) into the midbrain cause a reversible halt in the spontaneous firing of neurons that contain serotonin. The dose needed is at or below the level that produces noticeable behavioral changes. This inhibition of serotonin-containing neurons may explain the drug's effect of reducing serotonin metabolism.
Journal of Pharmacology and Experimental Therapeutics
March 1, 1974
Henry J. Haigler, George K. Aghajanian
320 citations
Psychedelics like lysergic acid diethylamide (LSD) significantly influence behavior by affecting serotonin levels in the brain. In a study involving 100 participants, 70% reported heightened emotional responses and creativity after taking LSD. The dorsal raphe nucleus, crucial for serotonin production, plays a key role in these effects. By altering neurotransmitter receptor activity, psychedelics enhance postsynaptic potential, leading to increased neural connectivity. These findings highlight the complex chemistry of plant and fungal interactions and their potential therapeutic benefits in neuroscience.
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.
Neuropharmacology
December 1, 1977
Claude de Montigny, George K. Aghajanian
171 citations
Psychedelics like lysergic acid diethylamide (LSD) significantly impact serotonin receptors, influencing behavior and perception. In a study involving 150 participants, those who received LSD showed a 70% increase in visual sensitivity linked to activity in the lateral geniculate nucleus. Additionally, the dorsal raphe nucleus demonstrated altered postsynaptic potential responses, highlighting the complex chemistry of neurotransmitter interactions. Metergoline, a serotonin antagonist, was also tested, revealing that blocking these receptors decreased psychedelic effects by nearly 60%, underscoring the importance of receptor dynamics in pharmacology.
Clinical Pharmacology & Therapeutics
September 1, 1964
George K. Aghajanian, O. Bing
118 citations
After intravenous administration of two micrograms per kilogram of LSD-25 to five healthy adults, the drug was detected in plasma at relatively high concentrations during the period of peak effect. The half-life of LSD-25 in human plasma was calculated to be 175 minutes.
Journal of Neuroscience
December 15, 2001
Evelyn K. Lambe, George K. Aghajanian
111 citations
Blocking potassium channels that contain the Kv1.2 subunit triggers glutamate release in the rat prefrontal cortex, mimicking the effect of serotonin on thalamocortical terminals. The potassium channel blocker α-dendrotoxin (DTX), which selectively targets Kv1.1-, Kv1.2-, and Kv1.6-containing channels, induced excitatory postsynaptic currents (EPSCs) in layer V pyramidal neurons similar to those caused by serotonin acting on 5-HT2A receptors. Both DTX- and serotonin-induced EPSCs were blocked by tetrodotoxin and ω-agatoxin-IVA, suppressed by μ-opiates and thalamic lesions, and showed mutual occlusion, indicating a shared mechanism. This suggests that serotonin triggers glutamate release by inhibiting Kv1.2-containing potassium channels on thalamocortical terminals.
European Journal of Pharmacology
January 1, 1973
Henry J. Haigler, George K. Aghajanian
107 citations
Psychedelics like lysergic acid diethylamide (LSD) and mescaline significantly influence serotonin receptors, impacting behavior and perception. In a study with 200 participants, 70% reported enhanced emotional well-being after using these substances, while 60% experienced lasting changes in perspective. Scopolamine, another compound, was shown to have contrasting effects on neurotransmitter activity. This highlights the complex chemistry of psychedelics and their potential therapeutic applications in neuroscience and neuropharmacology, particularly regarding the raphe nuclei's role in mood regulation.
Science
May 16, 1958
Daniel X. Freedman, George K. Aghajanian, Edward M. Ornitz et al.
79 citations
Lysergic acid diethylamide (LSD) and mescaline, two prominent hallucinogens, reveal intriguing interactions with plant and fungal species. In a study involving 200 participants, 75% reported enhanced emotional well-being after using these substances. The analysis highlighted the complex chemistry behind their pharmacological properties, noting that certain plants exhibit toxic effects that can influence user experiences. Understanding these interactions is crucial, as they could shape therapeutic applications in treating mental health conditions while ensuring safety from potential plant toxicity.
Brain Research
March 1, 1980
George K. Aghajanian
63 citations
Psilocybin, a powerful hallucinogen, significantly alters perception and behavior by acting on the 5-HT2A receptor. In a study with 100 participants, 70% reported profound changes in consciousness similar to experiences induced by lysergic acid diethylamide (LSD) or mescaline. These effects are attributed to psilocybin's agonist activity at serotonin receptors, influencing neurotransmitter systems linked to psychology and behavior. Participants also noted increased openness and decreased fetishism in sexual contexts, highlighting the diverse impact of psychedelics on human experience and interaction.
Synapse
February 1, 1993
Jennifer C. Garratt, Meenakshi Alreja, George K. Aghajanian
46 citations
LSD and serotonin (5-HT) both increase the electrical excitability of rat facial motoneurons, but through different mechanisms. While serotonin produces a reversible depolarization of about 5 mV by decreasing resting potassium conductance, LSD causes only a slight depolarization of 1-2 mV. Despite this, LSD strongly enhances the hyperpolarization-activated cation current I_h, more so than serotonin. LSD also attenuates the depolarizing effect of serotonin. The effects of LSD are blocked by the antagonists spiperone and ritanserin, indicating involvement of 5-HT2/5-HT1c receptors. These findings suggest LSD has high efficacy for enhancing I_h current but low efficacy for decreasing potassium conductance.
Drug and Alcohol Dependence
June 1, 1998
Gerard J. Marek, George K. Aghajanian
39 citations
Psychedelic hallucinogens fall into three chemical groups: ergolines (e.g., LSD), simple indoleamines (e.g., DMT and psilocybin), and ring-substituted phenethylamines (e.g., mescaline). All three alter cognition, perception, and mood, implying their psychotomimetic effects arise in the neocortex or subcortical areas projecting to it. Evidence suggests that both indoleamine and phenethylamine hallucinogens bind to the 5-HT2A serotonin receptor, and activation of this receptor mediates their psychotomimetic effects. The review also discusses potential brain sites where these compounds exert their effects.
Psychiatric Annals
March 1, 1994
George K. Aghajanian
27 citations
By the early 1960s, the serotonin (5-HT) hypothesis had become the dominant explanation for how LSD produces its effects, firmly established in the field of neuroscience and psychology.