Psychedelic Science Newsletter
Issue #7October 20, 20257 studies

Psilocybin vs. Lisuride: Why Only One Causes Hallucinogenic Effects

Psilocybin vs. Lisuride: Why Only One Causes Hallucinogenic Effects

Monday, Monday, October 20th Psychedelic Medicine Newsletter Issue #7

This week's research reveals surprising differences between psychedelic compounds, volunteer bias in clinical trials, and new therapeutic frameworks that could reshape mental health treatment.

🧠 Why Psilocybin Trips But Lisuride Doesn't

Scientists compared two drugs that both target the same brain receptor (5-HT2A) but produce completely different effects. In mice, psilocybin (0.3-3 mg/kg) caused the signature head twitch response that indicates psychedelic activity, while lisuride (0.1-0.5 mg/kg) didn't trigger this behavior at all.

  • Different brain pathways: Even though both drugs hit the same receptor, psilocybin primarily affected serotonin neurons while lisuride had stronger effects on dopamine neurons

  • Opposite therapeutic profiles: Psilocybin produced classic psychedelic effects, while lisuride improved coping behavior in stress tests without the hallucinogenic experience

  • Clinical implications: This explains why some 5-HT2A drugs become therapeutic psychedelics while others become anti-nausea medications

Why this matters: Understanding these differences could help scientists design targeted psychedelic medicines - some for breakthrough therapeutic experiences, others for symptom relief without the trip.

Key Findings

🎯 Psychedelic Research Has a Volunteer Problem

A study of 702 people found that those willing to participate in psychedelic research were dramatically more likely to have used psychedelics before. Previous users showed increased willingness to join unpaid surveys and drug administration studies, creating a bias where research participants aren't representative of the general population.

💡 People already familiar with psychedelics are overrepresented in studies, potentially skewing results about safety and effectiveness.

🌱 Group Ketamine Therapy Reaches 750+ Patients

The Roots To Thrive model has delivered ketamine-assisted therapy to over 750 participants through more than 2,000 sessions since 2018. This group-based approach combines Western clinical frameworks with Indigenous knowledge systems, focusing on community support rather than individual treatment.

💡 Scalable group therapy models could make psychedelic treatments accessible to more people while reducing costs.
Top 20% journal 🔗 Frontiers in Psychiatry 🗓️ Oct 7

🔗 Hypnosis and Psychedelics Share Key Features

Researchers found that people who respond well to psychedelics (those high in absorption and openness) also tend to be highly responsive to hypnosis. Both states produce similar changes in body sensations, vivid imagery, and transcendent experiences, though psychedelic effects last longer and are less controllable.

💡 Hypnotic responsiveness might predict who will benefit most from psychedelic therapy.

📊 New Scale Measures Ibogaine's Unique Dream-Like Effects

Scientists developed a 70-item scale to measure ibogaine experiences after testing 499 participants across two clinical settings. The scale captures seven distinct aspects including narrative visions, visual changes, and dissociation - effects that existing psychedelic questionnaires missed entirely.

💡 Each psychedelic produces such unique effects that we need specialized tools to measure and understand them properly.
Top 30% journal 🔗 PLoS ONE 🗓️ Oct 12

🧬 LSD Shows Promise for Treatment-Resistant Depression

LSD affects both serotonin and glutamate brain systems, potentially explaining why it produces rapid antidepressant effects that last beyond the drug's presence in the body. This dual mechanism could help the 30% of depression patients who don't respond to conventional antidepressants.

💡 LSD's unique brain mechanisms offer new hope for the millions with treatment-resistant depression.
🥉 Top 5% journal 🔗 Neuroscience and Biobehavioral Reviews 🗓️ Oct 10

💭 Veterans Express Cautious Interest in MDMA Therapy

When 30 veterans wrote stories about MDMA-assisted therapy for PTSD, at least one-third mentioned curiosity about the treatment alongside concerns about side effects and addiction potential. However, 10% showed clear misunderstandings about how the treatment actually works.

💡 Veterans are interested but need better education about psychedelic therapies to make informed decisions.

Implications

This week's research highlights both the promise and complexity of psychedelic medicine - from understanding why different drugs produce different effects to addressing practical challenges like volunteer bias and patient education. As these treatments move toward mainstream medicine, success will depend on matching the right compounds to the right patients while ensuring broad, representative research.

Studies in this issue

Primary sources used for this newsletter.

  1. Different effects of psilocybin and lisuride on serotonin and dopamine brain cells and behavior
    main storyProgress in neuro-psychopharmacology & biological psychiatry2025-10-12PMID 41077262
  2. How LSD May Work and Its Potential Use for Treating Depression
    key findingNeuroscience and biobehavioral reviews2025-10-11PMID 41076096
  3. The Ibogaine Experience Scale: Creating and testing a tool to measure different personal effects of ibogaine
    key findingPloS one2025-10-13PMID 41082525
  4. Questions and concerns about MDMA therapy for veterans with PTSD symptoms
    key findingJournal of psychoactive drugs2025-10-10PMID 41070441
  5. Group Ketamine-Assisted Therapy Program in a Community Setting: the Roots To Thrive Approach
    key findingFrontiers in psychiatry2025-10-08PMID 41058650
  6. How Hypnosis and Psychedelics Similarly and Differently Affect Conscious Experience
    key findingThe International journal of clinical and experimental hypnosis2025-10-08PMID 41061141
  7. How Volunteer Bias May Affect Psychedelic Research
    key findingJournal of psychoactive drugs2025-10-08PMID 41058595

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