LSD

links: Drugs reference:

• https://raypeatforum.com/community/threads/babies-experience-life-as-an-lsd-trip-as-a-result-of-their-high-metabolism.24941/
• [Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences]
  • drug-induced changes of conscious awareness (e.g., dissolving self-world boundaries or fractal distortion of visual perception) are linked to cortex-wide anatomical distributions of receptor density proxies. The dominant explanatory factor related ego-dissolution-like phenomena to a constellation of 5-HT2A, D2, KOR, and NMDA receptors, anchored especially in the brain’s deep hierarchy (epitomized by the associative higher-order cortex) and shallow hierarchy (epitomized by the visual cortex). 4-29-2021

LSD (Lysergic acid diethylamide) #

• Agonizes 5-HT2A, 5-HT2B, and 5-HT2C, partial agonist of 5-HT1A.
  • David Nichols in a presentation said it’s a fairly weak agonist on 5-HT2A— something like 30%.
• Histamine H2 antagonist (as are other hallucinogens). (Cyproheptadine was the most potent of all)
• Agonizes AMPAR and κ-Opioid Receptor, and antagonizes Acetylcholine -> mGluR2 antagonism -> PI3K-AKT-mTOR pathway -> hippocampal synaptogenesis
• Defining the histamine H2-receptor in brain: the interaction with LSD
• Increased thalamic resting‐state connectivity as a core driver of LSD‐induced hallucinations
  • LSD‐induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects
    • An important model suggested that hallucinogens disrupt thalamic gating of external and internal signals, leading to increased passage of information across the cortex: Serotonin research: contributions to understanding psychoses (good stuff)
• Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine
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• Psyhcedelics Promote Structural and Functional Neuroplasticity

• https://raypeatforum.com/community/threads/lsd-antagonizes-serotonin-and-glutamate-excitation.8854/

  • Antagonizes Serotonin excitation of single neurons, and Glutamate excitation of neurons which could be excited by 5-HT. LSD’s antagonism to serotonin is mediated through autoreceptor activation.

• H2 antagonist. R

• White FJ. Comparative effects of LSD and Lisuride…

  • Increases whole brain concentrations of 5-HT, but reduces synthesis and metabolism of it.
  • Central H1 antagonist.
  • Decreases 5-HIAA.
  • Increases Noradrenaline turnover.
  • Weak Dopamine agonist compared to Lisuride, even antagonizing at higher doses by increasing DA synthesis (How does that work? Autoreceptor binding affinity?)
  • Increases Homovanillic Acid levels.

• Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists

  • Facilitated activation of locus coeruleus neurons by sciatic nerve stimulation. https://serendipstudio.org/bb/neuro/neuro98/202s98-paper3/Frederickson3.html
  • LSD has a higher affinity for all the 5-HT receptors than serotonin - but it has a lower potency. This explains how it exhibits “antagonistic” actions while technically being an agonist. Are there other molecules like this? It seems strange how all these psychedelics just bind to 5-HT. Can this happen to other monoamines, or even something like acetylcholine.
  • 5-HT2 antagonists do not decrease the effects of LSD.

• 67.02mg/L water solubility.