Depression Treatment Breakthrough: The Return Of LSD In Modern Medicine

This article was originally published on Microdose Psychedelic Insights and appears here with permission.

As the search for effective treatments for depression continues, researchers have begun to revisit LSD as a treatment for depression. Emerging evidence suggests that LSD may offer a novel approach to treating depression by targeting the brain differently than traditional antidepressants. 

This article will delve into some studies that support the use of LSD for depression.

How LSD Affects the Brain

One of the primary ways LSD affects the brain is through its interaction with the serotonin system. Serotonin is a neurotransmitter involved in various physiological and cognitive processes, including mood regulation, appetite, and sleep. LSD has a strong affinity for the serotonin 2A (5-HT2A) receptors, which are densely concentrated in regions of the brain associated with cognition, perception, and mood (1).

When LSD binds to 5-HT2A receptors, it stimulates a cascade of intracellular signaling events, leading to the release of various neurotransmitters, including glutamate, dopamine, and norepinephrine (2). This neurotransmitter release is believed to contribute to the diverse array of cognitive, emotional, and perceptual effects induced by the drug.

LSD Research for Depression

Several recent studies have investigated the potential of LSD as a treatment for depression, with promising results.

Study on LSD molecules shows anti-depressant effects 

Researchers at UC San Francisco, UNC-Chapel Hill, Yale, Duke, and Stanford universities have discovered that LSD molecules can counter depression without inducing the typical hallucinogenic “trip.” By binding to serotonin 2A (5-HT2A) receptors in the brain, LSD enhances the production of brain-derived neurotrophic factor (BDNF), promoting neuroplasticity. The study found that administering a low dose of the compound reduced depressive symptoms without causing the traditional psychedelic experience, opening the door for further exploration of LSD’s potential as a treatment for depression.

LSD Microdosing trial 

In May 2022, MindBio Therapeutics announced the completion of its 12 month Phase 1 clinical trial microdosing LSD in 80 healthy participants. MindBio is developing a microdosing regimen using LSD to treat mental health disorders such as depression. At 2022’s Wonderland conference, MindBio presented more data from its trial, showing early data of the effectiveness of low-dose LSD for depression. 

• 1102 microdses (LSD/placebo) were administered in the trial with 100% adherence to regimen and no diversion of substances.
• Daily questionnaires showed credible evidence (>99% posterior probability) of increased ratings of “energy”, “wellness”, “creativity”, “happiness” and “connectedness” on dose days relative to non-dose days, which persisted when controlling for pre-intervention expectancy.

LSD Therapy for Major Depression 

The most recent and perhaps most significant research on LSD for depression came in April 2023. The team at University Hospital Basel published early results from a clinical trial entitled LSD Therapy for Persons Suffering From Major Depression: A Randomised, Double-blind, Active-placebo Controlled Phase II Study

The research team announced positive results from this trial, with patients receiving the high dose of LSD showing a decrease of 12.9 points (50% symptom reduction) vs a 3.6-point in the control dose. This was a significant reduction in symptoms that lasted for at least 16 weeks.

These positive results for treatment of depression could be used to strengthen the case for LSD treatment of anxiety, as the two conditions share comorbidities. 

This trial was at the University Hospital, Basel, Switzerland, with ownership rights to MindMed. More results from this study are expected later in 2023. 

The growing body of research on LSD and its potential as a treatment for depression is encouraging, but more extensive and controlled clinical trials are necessary to take this potential to the next level.