Psychedelic Science Newsletter
Issue #11November 17, 20257 studies

LSD microdosing cuts depression 59% in 8 weeks, while ketamine's antidepressant effects traced to brain adenosine surges

LSD microdosing cuts depression 59% in 8 weeks, while ketamine's antidepressant effects traced to brain adenosine surges

Monday, November 17th Psychedelic Medicine Newsletter Issue #11

This week brought groundbreaking insights into how psychedelics reshape mental health treatment, from tiny doses of LSD showing major depression improvements to scientists finally cracking the code on ketamine's rapid-acting mechanism.

🧬 LSD Microdosing Shows Major Promise for Depression Treatment

A small but significant study tracked 19 people with major depression as they took tiny doses of LSD (6-20 micrograms) twice weekly for 8 weeks. Here's what happened:

  • Depression scores dropped by 59.5% by the end of treatment, with improvements lasting up to 6 months

  • Most participants (15 out of 19) were already taking antidepressants, suggesting microdosing may work alongside existing treatments

  • Only one person dropped out due to anxiety, and no serious side effects occurred - notably, this was the first study to check for heart valve problems after repeated psychedelic use

Why this matters: While the sample was small and there was no placebo group, these results suggest microdosing could offer a gentler alternative to full psychedelic experiences while still providing substantial mental health benefits.

🎖️ Top 10% journal 🔗 Neuropharmacology 🗓️ Nov 7

Key Findings

🔬 Ketamine’s Antidepressant Effect Traced to Adenosine Surges

Researchers finally figured out how ketamine works so quickly as an antidepressant—and it's not what they expected. Using mouse models, they discovered ketamine triggers massive surges of adenosine (the brain chemical that makes us sleepy—caffeine works by blocking its receptors) in mood-regulating areas like the prefrontal cortex and hippocampus. When they blocked adenosine receptors, ketamine stopped working entirely. The team even developed new ketamine-like compounds that boost adenosine more effectively, showing better antidepressant effects with fewer side effects.

💡 This discovery could lead to safer, more targeted depression treatments and explains why ketamine works when other antidepressants fail.
🏆 Top 0.1% journal 🔗 Nature 🗓️ Nov 5

💊 MDMA Shows Strong Results for PTSD Despite FDA Setback

A systematic review of 7 randomized trials involving 280 adults with PTSD found that 5 out of 6 studies showed significant improvement with MDMA-assisted therapy. Between 41.7% and 85.7% of MDMA participants no longer met PTSD criteria after treatment, compared to just 25-33% in placebo groups. The treatment appeared well-tolerated across studies, even though the FDA recently voted against approval citing safety concerns.

💡 The FDA’s rejection wasn’t about weak results. MDMA-assisted therapy worked so noticeably that many participants could tell they’d received it—blurring the placebo line. Regulators cited this “functional unblinding,” along with safety and misuse concerns, as reasons to pause approval despite strong evidence of benefit.

🎯 Ketamine Plus EMDR Therapy Cuts PTSD Symptoms

Eight clients with PTSD received a novel treatment combining low-dose sublingual ketamine (37.5-75mg) with EMDR trauma therapy. After just 4 sessions, PTSD symptom scores dropped from an average of 15.5 to 9.88, while functional impairment scores fell from 8.5 to 5.25. Participants reported reduced fear, increased self-compassion, and minimal side effects from the combined approach.

💡 Combining ketamine with established trauma therapies may create synergistic effects that enhance memory reprocessing and accelerate recovery.
🎖️ Top 10% journal 🔗 European Journal of Psychotraumatology 🗓️ Nov 4

📊 Large Analysis Shows Psychedelics Reduce Substance Abuse Risks

A massive study of over 3.2 million patients with substance use disorders found that those who used psychedelics (primarily ketamine) had significantly lower rates of overdose (52% reduction), relapse (32% reduction), and hospitalizations (24% reduction) compared to those receiving no treatment. The strongest protective effects occurred when psychedelics were combined with anesthetic care and outpatient services.

💡 Psychedelics are often lumped together with addictive drugs, yet their effects may move in the opposite direction—reducing relapse, overdose, and hospitalization risk rather than fueling it.
Top 20% journal 🔗 Frontiers in Psychiatry 🗓️ Nov 10

🧪 Naturalistic LSD Use Linked to Lower Alcohol Problems

Analysis of a nationally representative sample of 139,524 people found that those who used LSD in the past year had 30% lower odds of having alcohol use disorder and 15.7% fewer alcohol-related symptoms. Interestingly, MDMA and ketamine use showed no such protective associations, suggesting LSD may have unique properties affecting alcohol consumption patterns.

💡 LSD's apparent protective effect against alcohol problems may point to specific therapeutic mechanisms worth investigating in controlled clinical trials.

⚖️ Meta-Analysis Reveals Mixed Results for Psychedelic Mental Health Treatments

A comprehensive review of 30 randomized trials with 1,480 participants found that MDMA significantly reduced PTSD symptoms, while psilocybin and other serotonergic psychedelics showed moderate effects for depression and anxiety. However, the psychedelics showed no benefit for alcohol use disorder or ADHD. The analysis noted that 83.3% of studies had high risk of bias, and only MDMA for PTSD reached moderate certainty of evidence.

💡 While promising for specific conditions, psychedelic therapies need more rigorous research to establish which treatments work best for which mental health conditions.
🥉 Top 5% journal 🔗 European Neuropsychopharmacology 🗓️ Nov 8

Implications

This week's research reveals psychedelics are entering a more nuanced phase of scientific understanding. While LSD microdosing and ketamine's adenosine mechanism offer promising therapeutic pathways, the mixed results across different conditions and compounds suggest we're moving beyond the initial excitement toward more precise, evidence-based applications. The challenge now is translating these mechanistic insights into safer, more targeted treatments while maintaining the therapeutic benefits.

Studies in this issue

Primary sources used for this newsletter.

  1. LSD microdosing in major depression: results from an open-label trial
    main storyNeuropharmacology2025-11-07PMID 41202873
  2. Effectiveness, dropout rates, and safety of serotonin-related psychedelics and MDMA for treating mental health conditions
    key findingEuropean neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology2025-11-08PMID 41205366
  3. MDMA-Assisted Therapy for PTSD: A Review of Controlled Clinical Trials
    key findingJournal of psychoactive drugs2025-11-05PMID 41190692
  4. Ketamine and EMDR Therapy Together for PTSD: Studying How Drug Treatment and Talk Therapy Work Together
    key findingEuropean journal of psychotraumatology2025-11-04PMID 41186022
  5. Links between psychedelic use and negative outcomes in people with substance use disorders using real-world health records
    key findingFrontiers in psychiatry2025-11-10PMID 41210131
  6. How Psychedelic Use Is Linked to Alcohol Use Disorder in a National Sample
    key findingJournal of psychoactive drugs2025-11-10PMID 41208129
  7. Adenosine signals may help ketamine and ECT relieve depression
    key findingNature2025-11-05PMID 41193806

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