Testing the Effects of LSD Microdoses on Mood and Cognitive Functioning

Post by Lincoln Tracy

What's the science?

Lysergic acid diethylamide (LSD) is a hallucinogenic drug commonly used for recreational purposes. The psychoactive effects of LSD are primarily thought to arise through its ability to bind to serotonin receptors, like many other antidepressants. Since the 1950’s, there have been more than a thousand studies investigating the use of LSD as a potential treatment for depression. However, many of these studies used LSD in combination with psychotherapy and did not have appropriate control groups—meaning that it was not possible to isolate the effects of the drugs from the psychotherapy. In recent years there has been a huge spike in public interest in using ‘microdoses’ (between five and 20 micrograms) of LSD to improve mood and cognitive function. LSD microdoses have great therapeutic potential, as the higher doses used in previous studies are impractical for long-term administration due to perceptual distortions and impaired inhibitory control. This week in Biological Psychiatry, Bershad and colleagues examined the mood-altering, psychological, and behavioral effects of three different microdoses of LSD in young, healthy adults in a double-blind and placebo-controlled fashion.

How did they do it?

The authors recruited 20 healthy volunteers (including 12 women) as part of their study to test the effects of LSD microdoses on human behavior. Each volunteer took part in four testing sessions, each separated by at least seven days. In each testing session, the volunteers took one of four different doses of LSD—either zero micrograms (the placebo control condition), 6.5 micrograms, 13 micrograms, or 26 micrograms. Volunteers completed questionnaires about the perceived drug effects, their mood and their state of consciousness. They also had their heart rate and blood pressure recorded before they took LSD, and again at 30 and 90 minutes post drug administration. In each session volunteers also completed several behavioral and cognitive tasks: a dual N-back task (a measure of working memory), the Digit Symbol Substitution Task (a measure of cognitive functioning), “Cyberball” (a measure of simulated social exclusion), the Emotional Images Task, and a Remote Associations Task (measuring creativity).

What did they find?

Volunteers reported that the 13- and 26-microgram doses of LSD significantly increased the feeling of having taken a drug, with the 26-microgram dose also increasing the sensation of feeling high and liking the drug. This higher dose also resulted in higher ratings of disliking the drug, and increased feelings of vigor and anxiety. LSD also showed subtle dose-dependent effects on altering states of consciousness including ‘increased experience of unity' and ’increased blissful state.’ The two higher microdoses of LSD also increased systolic blood pressure, with the 26-microgram dose increasing diastolic blood pressure. Increasing the dose of LSD reduced the positivity ratings of positive pictures during the Emotional Images Task. None of the LSD microdoses had effects on heart rate or body temperature. LSD also had no effect on the dual N-back task, the Digit Symbol Substitution Task, Cyberball, or the Remote Associations Task performance.

What's the impact?

This study observed that small doses of LSD resulted in moderate increases on drug effect rating scales yet had very subtle effects on behavior and cognitive function. A 13-microgram dose (microdose) of LSD appears to be the optimal dose for repeat dosing studies.The findings from this study—the first to test multiple microdoses of LSD in a within-subjects, placebo-controlled manner—will help to guide research into repeat microdosing in clinical populations. Further research in clinical populations involving single and repeat dosing is required and may enhance our understanding of the neural and behavioral processes underlying depressed mood.     

Bershad et al. Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry (2019). Access the original scientific publication here.