Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study

This trial (n=32) assessed the safety, tolerability, pharmacokinetics, and subjective effects of varying doses of LSD in healthy adults within a novel intervention paradigm. Participants received 50 (n = 3), 75 (n = 7), 100 (n = 3) LSD, 50 µg followed by 75 µg LSD (n = 9) 1 week apart, or placebo followed by a 75 µg LSD (n = 10) 1 week apart. Twenty-eight per cent of participants experienced a mild adverse event while no serious adverse events were reported. This data indicates that LSD is safe and well-tolerated.


Background: Classic psychedelics hold promise as therapeutics for psychiatric disorders, but require scalable intervention protocols. This proof-of-concept study evaluated the safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg lysergic acid diethylamide (LSD) in healthy adults within a novel intervention paradigm.

Methods: Up to three participants were administered LSD on the same day in separate rooms, each with a single attendant, after 1 day of preparation. An open-label design and a double-blind placebo-controlled design were used.

Results: Ninety-one per cent of participants completed the study. Thirty-two adults (mean age = 28.8 years) received 50 (n = 3), 75 (n = 7), 100 (n = 3) LSD, 50 µg followed by 75 µg LSD (n = 9) 1 week apart, or placebo followed by a 75 µg LSD (n = 10) 1 week apart. There were no serious adverse events. Twenty-eight per cent of participants experienced at least one expected mild adverse event, with one expected moderate adverse event. The maximum blood plasma levels occurred between 1.2 and 2 h post-administration, with an apparent half-life between 2.8 and 4.3 h. LSD largely induced greater subjective effects versus placebo.

Conclusion: In the current novel intervention paradigm, 50, 75, and 100 µg LSD are tolerable with favourable safety profiles in healthy adults, only mild adverse events during the day of drug administration, and mystical-type subjective experiences. Future studies are needed to evaluate the safety, tolerability, subjective effects, and cost-effectiveness in clinical populations.”

Authors: Neiloufar Family, Peter S. Hendricks, Luke T.J. Williams, David Luke, Erwin Krediet, Emeline L. Malliet & Shlomi Raz


When we think of integrating psychedelic-assisted psychotherapy (PAP) into clinical practice, it may be limited in its reach due to the labour-intensive nature of the current PAP paradigm. In the current paradigm, patients require many hours with psychotherapists in preparation sessions as well as integration sessions following the psychedelic experience. Together, these intensive approaches may render psychedelics expensive and difficult to access, especially for those living with economic disadvantages. Thus, in order to scale PAP, a different approach may be needed.

In the present study, researchers tested the safety and tolerability of escalating doses of LSD in healthy subjects within a novel intervention paradigm which was considered to be more scalable than the current PAP treatment protocols. This study, sponsored by Eleusis, was divided into two parts: 1) an open-label dose-escalating study involving experienced psychedelic users to evaluate the tolerability and pharmacokinetics (PK) of different LSD doses and determine the appropriate LSD doses for use in the second part of the study; 2) a double-blind placebo-controlled part to allow for the comparison of protocol measurements taken during LSD administration to placebo as well as within-subject comparison of different LSD doses.

The Novel Intervention Paradigm

  • Participants spent full days at the research site, and their participation was framed around exploring creativity vis-à-vis a work-related problem they described at their screening visit. This framing required participants to focus on improving an aspect of their life (i.e. productivity on a professional problem) and provided an opportunity to develop an operational protocol for an interventional trial.
  • The specific problem-solving aspect of this trial sets it apart from previous studies administering classic psychedelics to healthy participants which have largely been laboratory studies with the sole objective of evaluating safety, pharmacokinetics, and related assessments and/or neuroimaging.
  • The design used a single attendant to assist each participant during each drug administration, employed remote monitoring of the rooms used for drug administration, fostered group interactions, and a strong collaborative ‘interpersonal atmosphere’ over a single day prior to drug administration and required no ongoing interaction between participants and attendants after the drug administration day.

Part One

  • In part 1, 13 participants were enrolled and received 50µg (n=3, no women, mean age = 28), 75µg (n=7, one woman, mean age = 28) or 100µg (n=3, no women, mean age = 32) LSD on a single occasion.

Part Two

  • In part 2, the experimental group (n=9, two women, mean age = 27) received two sequential single doses of LSD (50µg followed by 75µg), with dosing separated by seven drug-free days.
  • The placebo-controlled group (n=10, one woman, mean age = 31) received a placebo followed, after seven drug-free days, by a single dose of 75µg LSD.

For both parts 1 and 2, altered states of consciousness were measured using three questionnaires administered at the end of the day of the drug administration session after dinner: the five-dimensional altered states of consciousness (ASC) scale, the ego dissolution inventory (EDI), and the mystical experience questionnaire (MEQ).

The Findings

  • LSD was found to be well tolerated in the population studied, with 30 of 33 participants (91%) completing all aspects of the current study.
  • There were no serious adverse events while 28% of participants (n=9) experienced at least one expected treatment-emergent adverse advents which included vomiting/nausea, headache and fatigue, among others.
  • Compared to placebo, LSD largely produced greater subjective effects than placebo reflected in elevations in ASC, EDI, and MEQ scores with the authors stating that the current report is the first to demonstrate such elevations produced by 50µg LSD specifically.
  • A review of the safety and tolerability suggests that the aforementioned novel intervention paradigm may not affect the physical or psychological safety of healthy participants while the observed subjective effects suggest these changes may not inhibit the transcendent, mystical-type experiences that are thought to mediate therapeutic outcomes.
  • Qualitative analysis of participants’ accounts can be found here.


  • The sample only included healthy participants. Clinical populations may require closer monitoring to ensure patient safety and the best possible therapeutic outcomes. Thus, all components of the intervention paradigm that were tested in this study would need to be re-evaluated in clinical samples before implementation in patient populations.
  • The overall sample size is small (32).
  • Participants were informed of the identity of the drug, raising the possibility of expectancies influencing the results.
  • Some components of the novel paradigm may actually be more costly than currently proposed PAP e.g full days at the study site, overnight stays, provision of meals.

Ultimately, the findings of the present study support the feasibility of new treatment design protocols for drug administration and open the door for larger studies designed to evaluate further refinements and additions to these new treatment designs for the safe and cost-efficient delivery of PAP.

Summary of Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study


LSD is a classic psychedelic that induces alterations in consciousness at doses currently being considered for treatment of psychiatric disorders. However, the sensoriperceptual effects of LSD at moderate-to-high doses could limit their viability as accessible treatments in psychiatric care.

LSD is generally regarded as safe when administered in clinical settings, but can cause anxiety, derealization, depersonalization, emotional distress, feeling abnormal, feeling cold, having illusions, difficulty concentrating, and headache. It also increases suggestibility, which may account for its therapeutic efficacy.

To access this content, you must purchase one of the following memberships: Sprout Membership, Pro Membership, Pro Membership Unlimited, Business Membership or Business Membership Unlimited. The membership will give you access to exclusive data, including summaries of psychedelic research papers, extended company info, and our member-only visualisations. Save yourself multiple hours each week by accessing Blossom’s resource library.


Institutes associated with this publication

Eleusis is a clinical-stage life sciences company that studies and develops psychedelic drugs for therapeutic use. Since 2013 the company has been researching psychedelics and is now developing ELE-Psilo (psilocybin) for depression that is in Phase I.

Compound Details

The psychedelics given at which dose and how many times

LSD 50 - 100
μg | 2x

Linked Clinical Trial

A Dose-Ranging Study of 50 µg to 100 µg LSD in Healthy Volunteers
This Phase I study explored the safety, tolerability, pharmacokinetics, and pharmacodynamics of low doses of Lysergic Acid Diethylamide (LSD) ranging from 50 µg to 100 µg.