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Low Dose LSD for Depression Treatment: Preliminary Efficacy (2023 Study)

Recent research exploring the use of low doses of LSD (Lysergic acid diethylamide) in treating depression marks a significant shift in the psychiatric landscape.

This innovative approach seeks to understand and harness the potential therapeutic benefits of psychedelics, which were once stigmatized and largely overlooked in clinical settings.


  • Study Design: The research employed a randomized, double-blind, crossover design to investigate the effects of a 26 µg dose of LSD on individuals with varying levels of depressive symptoms.
  • Participant Groups: Participants were divided based on their Beck Depression-II inventory (BDI) scores into two groups: high BDI (≥17) and low BDI (<17).
  • Findings: The study reported that individuals in the high BDI group experienced significant improvements in mood and subjective well-being after receiving LSD, compared to the placebo group.
  • Implications: These results contribute to a growing body of evidence suggesting the potential of psychedelics like LSD as a treatment for depression, challenging traditional treatment approaches and offering new hope for patients.

Source: Neuropsychopharmacology (2023)

LSD for Psychiatric Disorders (Overview)

Lysergic acid diethylamide (LSD) has traversed a unique journey from its synthesis in 1938 to its controversial role in the mid-20th century, leading to its current resurgence in psychiatric research.

Once widely explored for its potential therapeutic applications, LSD became stigmatized and heavily regulated.

However, recent scientific endeavors are rekindling interest in its therapeutic potential, especially for psychiatric disorders such as depression, anxiety, post-traumatic stress disorder (PTSD), and substance addiction.

This renewed interest in LSD for psychiatric treatment stems from a growing body of research that highlights its potential benefits.

Unlike traditional pharmacotherapy, which often targets specific neurotransmitter systems, LSD offers a novel approach by profoundly altering perception and cognitive processes, which could be crucial in treating various psychiatric conditions.

LSD’s Mechanism of Action & Therapeutic Potential in Depression

LSD’s primary mechanism is its agonist activity at serotonin receptors, particularly the 5-HT2A receptor.

This interaction leads to altered neural connectivity and neurotransmission, resulting in the characteristic psychedelic experiences.

From a therapeutic perspective, LSD’s ability to induce a flexible cognitive state is key.

This flexibility can disrupt entrenched negative thought patterns, a common issue in psychiatric disorders.

LSD also enhances emotional empathy and sociality, potentially benefiting conditions marked by social withdrawal.

LSD’s impact on neuroplasticity – the brain’s ability to reorganize and form new neural connections – offers another avenue for its therapeutic potential.

This property may facilitate the ‘rewiring’ of dysfunctional neural pathways associated with psychiatric disorders.

Why use low-dose LSD for depression?

LSD’s effects are profoundly dose-dependent.

Higher doses can lead to significant alterations in perception and consciousness, while lower doses, or ‘microdoses’, are associated with subtle changes in mood and cognition.

Advantages of Low-Dose LSD:

  • Safety: Lower doses minimize the risk of adverse psychological reactions and intense perceptual disturbances.
  • Functional Integration: Microdosing allows individuals to maintain daily functionality while potentially reaping LSD’s mood-enhancing and cognitive benefits.
  • Therapeutic Viability: Low doses can be more easily integrated into therapeutic settings, offering a balance between therapeutic effects and manageable side effects.

Low Dose LSD for Depression (2023 Study)

Molla et al. published a study investigating the effects of low-dose LSD for depressed mood in Neuropsychopharmacology.


The primary goal of this study was to investigate the acute and sub-acute effects of a low dose of LSD (26 µg) on mood and subjective experiences in individuals with varying levels of depressive symptoms.


  • Design: The study employed a randomized, double-blind, crossover design.
  • Participants: 39 adults were divided into two groups based on their scores on the Beck Depression-II inventory (BDI): a high BDI group (scores ≥17, n=20) and a low BDI group (scores <17, n=19).
  • Procedure: Each participant received a single low dose of LSD (26 µg) and a placebo in two separate 5-hour laboratory sessions, with a minimum one-week interval between sessions.
  • Measurements: Subjective effects, physiological responses, and mood measures were regularly assessed during the sessions. Additionally, tests for creativity and emotion recognition were conducted at the peak effect times. Follow-up assessments of BDI scores and mood ratings were conducted 48 hours after each session.


  • Overall Effects: LSD at 26 µg generally produced mild physiological and subjective effects in both groups.
  • High BDI Group: This group reported more significant acute effects from LSD compared to placebo. These included higher ratings of vigor, elation, and positive scales on a psychedelic effects measure (5D-ASC). Notably, there was a more substantial decline in BDI depression scores 48 hours after taking LSD compared to placebo.
  • Low BDI Group: The effects in this group were less pronounced and did not show a significant difference from placebo.


  • Sample Size: A relatively small sample size may limit the generalizability of the findings.
  • Short-term Assessment: The study focused on acute and sub-acute effects, so long-term implications remain unclear.
  • Specific Dose: Only one low dose of LSD was tested, so the findings may not apply to different doses.
  • Self-Selection Bias: Participants who are open to using psychedelics may have different baseline characteristics compared to the general population.

What are the implications of this study?

The study’s findings indicate that low doses of LSD can have significantly positive effects on mood and subjective experiences, particularly in individuals with mild to moderate depressive symptoms.

These results add to the growing body of research suggesting potential therapeutic benefits of psychedelics in mental health, specifically for mood disorders like depression.

  • Clinical Applications: The observed mood improvements post-LSD administration in the high BDI group suggest potential therapeutic applications for psychedelics in treating depression.
  • Psychedelic-Assisted Therapy: This research could pave the way for further studies into psychedelic-assisted therapies, where controlled doses of substances like LSD are used in conjunction with psychotherapy.
  • Understanding of Psychedelic Effects: The study contributes to a better understanding of how low doses of psychedelics affect mood and consciousness, especially in individuals with depressive symptoms.
  • Public Perception and Policy: These findings could influence public perception of psychedelics, potentially leading to changes in drug policy, especially regarding their medical and therapeutic use.
  • Further Research: The study underscores the need for more extensive, long-term research to explore the potential benefits and risks of using psychedelics in mental health treatment, including investigations into different dosages and long-term effects.

Safe Use of LSD in Psychiatric Treatment

Controlled Setting: Any therapeutic use of LSD should occur in a controlled, supervised clinical setting. This ensures the safety and well-being of the patient, allowing for immediate intervention if adverse reactions occur.

Screening and Monitoring: Patients should undergo thorough psychological screening before LSD therapy. Continuous monitoring during and after dosing is crucial to assess the drug’s effects and the patient’s mental state.

Integration Therapy: LSD treatment should be part of a broader therapeutic plan, including psychotherapy. Post-session integration sessions can help patients process their experiences and translate insights into meaningful changes in their lives.

Legal and Ethical Considerations: It’s important to consider the legal status of LSD and ethical implications of its use. Research and treatment should comply with regulatory standards and ethical guidelines.

Risks & Side Effects of Using LSD in Psychiatry for Depression

General Risks & Side Effects

Psychological Effects: Even at lower doses, LSD can cause significant psychological effects. These can include anxiety, confusion, and unpredictable emotional swings. In some cases, individuals may experience intense and disturbing thoughts or feelings, known as a “bad trip”.

Perceptual Distortions: While less intense at lower doses, LSD can still cause perceptual distortions. This might include visual hallucinations or altered sensory experiences, which can be disorienting or distressing for some individuals.

Long-term Effects: There is limited research on the long-term effects of repeated LSD use, even at low doses. Potential concerns include the risk of persistent psychological changes or the development of hallucinogen persisting perception disorder (HPPD), where individuals experience flashbacks or ongoing visual disturbances.

Dependence and Abuse: Although LSD is not considered addictive in the traditional sense, there is a potential for psychological dependence, especially in individuals with a history of substance abuse.

Importance of Patient Selection & Cautious Use

Screening for Susceptibility: Careful screening is crucial to identify individuals who may be at higher risk for adverse reactions. This includes those with a personal or family history of psychosis or bipolar disorder, as LSD can exacerbate these conditions.

Setting and Supervision: LSD should only be used in a controlled, clinical setting under the supervision of trained professionals. This ensures that any negative reactions can be promptly and effectively managed.

Informed Consent: Patients must be fully informed about the potential risks and benefits of LSD therapy. Understanding these factors allows them to make an informed decision about their treatment.

Monitoring Mental Health: Continuous monitoring of the patient’s mental health is essential during LSD therapy. This includes pre-treatment assessments, close observation during the session, and follow-up care to address any psychological effects.

Ethical Considerations: The use of LSD in therapy must adhere to strict ethical guidelines. This includes ensuring that the treatment is in the patient’s best interest and that they are not subjected to any undue risk.

Future Directions in LSD Research for Depression

The growing interest in using LSD for treating depression opens several avenues for future research.

These directions not only aim to solidify the understanding of LSD’s therapeutic potential but also address the complexities and challenges associated with its use.

1. Longitudinal Studies

To understand the long-term effects of LSD on depression.

Conducting longitudinal studies that track the mental health outcomes of patients over extended periods post-LSD therapy.

This will provide insights into the durability of its effects, potential long-term risks, and the necessity of repeated doses.

2. Dosing & Administration

To optimize dosing strategies for maximum therapeutic benefit with minimal side effects.

Research should focus on refining dosing protocols, including determining the most effective dose range for treating depression, frequency of administration, and the role of booster sessions.

3. Mechanistic Studies

To gain a deeper understanding of the biological and neurological mechanisms by which LSD alleviates depressive symptoms.

Utilizing advanced neuroimaging techniques and biomarker analyses to study changes in brain activity, connectivity, and neurochemistry associated with LSD administration in depressed individuals.

4. Comparative Studies

To evaluate the efficacy of LSD against existing treatments for depression.

Conducting comparative studies that assess the effectiveness of LSD in comparison to standard antidepressants, psychotherapy, or other emerging treatments like ketamine.

5. Personalized Medicine

To identify which subgroups of depression patients are most likely to benefit from LSD therapy.

Investigating the influence of genetic, environmental, and psychological factors on the response to LSD.

This could involve exploring biomarkers that predict treatment response and tailoring LSD therapy to individual patient profiles.

6. Integration with Psychotherapy

To explore how LSD can be best integrated with psychotherapy.

Developing and testing integrated treatment models that combine LSD with various forms of psychotherapy, such as cognitive-behavioral therapy (CBT) or mindfulness-based approaches.

7. Safety & Risk Management

To establish comprehensive safety protocols for LSD therapy.

Research should focus on refining guidelines for patient screening, monitoring during therapy, and managing potential adverse effects, especially in diverse populations with varying health conditions.

8. Legal & Ethical Frameworks

To address the legal and ethical implications of using LSD in clinical settings.

Collaborating with policymakers, ethicists, and legal experts to create frameworks that enable safe and regulated use of LSD in psychiatric treatment while addressing societal concerns.

Takeaway: LSD for Depression & Psychiatric Disorders

The exploration of LSD as a therapeutic tool in psychiatry represents a convergence of historical perspective, scientific inquiry, and clinical innovation.

While challenges and controversies remain, the potential of LSD to offer significant benefits in psychiatric treatment is gaining empirical support.

Future research, focused on understanding its mechanism of action, optimizing dosing strategies, and ensuring safe and ethical use, will be crucial in determining LSD’s role in modern psychiatry.

This journey from a stigmatized substance to a potentially revolutionary therapeutic agent underscores the evolving nature of psychiatric treatment and the importance of re-evaluating past assumptions in light of new evidence.


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