LSD Neuroscience - David E. Nichols

MAPS・2 minutes read

Research chemicals are increasingly used for initial psychedelic experiences, with LSD interacting with various receptors to induce unique effects. Studies on psychedelics focus on receptor interactions, including with serotonin receptors, and the Institute in Zurich conducts significant clinical research with minimal overhead costs.

Insights

  • Research chemicals are increasingly being used as individuals' first exposure to psychedelics, prompting a speaker to acknowledge their responsibility as some of these substances were derived from their work, highlighting the evolving landscape of psychedelic research and consumption.
  • The discovery of LSD and serotonin in the brain has significantly transformed the understanding of psychiatric disorders, shifting the focus from environmental factors like poor parenting to neurochemistry, showcasing the pivotal role of psychedelics in revolutionizing neuroscience and mental health paradigms.

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  • What are psychedelics?

    Psychedelics induce altered states of perception and feeling.

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Summary

00:00

Psychedelics: Research, Effects, and Neuroscience Insights

  • Research chemicals are becoming more common as people's first exposure to psychedelics, and the speaker feels a sense of responsibility as some of these chemicals were taken from their publications.
  • To become a researcher, one must inform patients about new research, refer patients to clinical studies, develop research strategies, and evaluate research.
  • The discovery of LSD and serotonin in the brain revolutionized neuroscience, shifting the understanding of psychiatric disorders from poor parenting to neurochemistry.
  • Psychedelics are unique in their ability to induce altered states of perception, thought, and feeling, not experienced otherwise except in dreams or religious experiences.
  • An exponential increase in published clinical studies on psychedelics has occurred since 2010, indicating a growing interest and impact in the field.
  • The key brain receptors for psychedelics are the serotonin 2a and 2c receptors, with tryptamines also activating the 1a receptor.
  • LSD's unique potency and effects stem from its interaction with various receptors beyond just serotonin 2a and 2c.
  • Psychedelics like LSD induce signaling within brain cells by binding to serotonin receptors and causing changes in protein shapes and signaling pathways.
  • The serotonin 2a receptor, essential for psychedelic effects, is highly expressed in brain structures involved in perception and consciousness, influencing sensory processing and consciousness.
  • Animal models are used in pharmacology to study drug effects on systems in the body, but no animal model can fully replicate the experiences seen in humans with psychedelics.

15:17

Psychedelics and Research Chemicals: Effects and Risks

  • In the fight-or-flight response, the heart beats faster due to the release of epinephrine, stimulating beta 1 receptors in the heart.
  • Psychedelics are ideal for studying consciousness and its perturbation effects.
  • Drug discrimination technique involves training rats to press levers for food pellets based on drug administration.
  • Rats trained with LSD can reliably recognize the effects of the drug through lever pressing.
  • Drug discrimination assay correlates relative potency of compounds compared to LSD in rats and humans.
  • Compound 25i-NBOMe is extremely potent, with overdose risks leading to deaths.
  • Affinity of compounds to receptors is affected by structural modifications, such as adding benzyl groups.
  • Research focuses on modeling receptor interactions of potent compounds like 25i-NBOMe.
  • Synthetic research chemicals, including psychedelics, psychostimulants, and entactogens, have varying effects and risks.
  • Lifetime use of psychedelics in the US exceeds 30 million people, with distinct effects and toxicity profiles for different classes of research chemicals.

30:00

Pharmacology of neurotransmitter systems and receptors

  • Pharmacology is determined by the substituents on the aromatic ring interacting with serotonin, dopamine, or norepinephrine.
  • G-protein coupled receptors like serotonin 2a receptor are bound together and coupled to intracellular signaling.
  • Transmitter reuptake transporters for dopamine, norepinephrine, and serotonin conserve and reuse transmitters, with substances like cocaine blocking these transporters.
  • MDMA and amphetamine displace stored dopamine, serotonin, norepinephrine, causing them to spill out in a reverse direction through transporters.
  • Ketamine interacts with ionotropic glutamate receptors, a third type of target.
  • Research chemicals target either reuptake transporters or g-protein coupled receptors, with psychedelics and synthetic cannabinoids interacting with gpcr.
  • Hallucinogens have affinity for serotonin 2a receptor, leading to generalization in LSD-trained rats.
  • Psychostimulants increase locomotor activity in rats and can be self-administered, producing reward qualities.
  • Intact agents, like MDMA, differ from psychostimulants by affecting serotonin systems more than norepinephrine and dopamine.
  • MDMA and its derivatives affect serotonin and dopamine release, with some compounds having low dependence liability compared to psychostimulants.

45:03

Psychedelics and Stimulants: A Research Overview

  • Entheogen Xanthian covers a broad category including psychedelics and psychostimulants.
  • Psychedelics typically have a 2,5-dimethoxy substitution on the ring.
  • Compounds like Fly and Dragonfly series are named based on their structures.
  • Substitution on compounds determines their pharmacology.
  • 2C-T-7 is classified as a psychedelic due to its ortho-methoxy substitution.
  • Methalone is a stimulant or an intact agent.
  • Synthetic cannabinoids like JWH compounds can be toxic and potent.
  • Research chemicals like 25i and BOM can be dangerous and unpredictable.
  • Conducting research on psychedelics requires a detailed protocol and justification.
  • Obtaining pure drugs for research purposes can be challenging and costly.

59:42

Psychedelic Research Institute: Funding, Findings, Stability

  • Founded in 1993, the institute has published over 50 publications and spent $3.4 million on research, primarily focused on clinical research in Zurich.
  • The institute's funding primarily goes towards research, with minimal overhead costs, allowing for significant achievements over the years.
  • The research was funded by the National Institute on Drug Abuse for 28 years, with a one-year extension, enabling substantial progress in understanding psychedelic compounds.
  • The complexity of the pharmacologic hypothesis behind the varying effects of different psychedelic compounds is attributed to multiple receptors, signaling pathways, and agonist/antagonist interactions.
  • The serotonin 2a receptors play a crucial role in sensory filtering in the brain, particularly in the thalamus, affecting information processing and perception.
  • The effects of psychedelic compounds on gut function are linked to serotonin release in the gut, stimulating contractions and potentially causing gastrointestinal effects.
  • The stability of LSD at room temperature is confirmed, with LSD stored in the dark at ambient temperature remaining stable for up to 30 years.
  • The potential impurities in LSD on blotter form are unlikely to cause harm due to the unique nature of LSD and the minimal quantities required for adverse reactions.
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