In a groundbreaking study, researchers at the University of Chicago have discovered that low doses of lysergic acid diethylamide (LSD), a psychedelic drug, may have potential antidepressant effects in individuals showing mild to moderate depressive symptoms. This new insight could pave the way for alternative treatments in mental health care. The findings have been published in the journal Neuropsychopharmacology.
For years, depression has remained a significant challenge in mental health, with traditional treatments like medications and psychotherapy not always effective for all patients. This gap in treatment efficacy has spurred interest in alternative therapeutic approaches. Recently, the focus has shifted towards psychedelic compounds like psilocybin (found in magic mushrooms) and LSD.
LSD is a powerful, synthetic psychedelic drug known for its profound effects on perception, emotions, and thoughts. Originally synthesized in 1938, it gained prominence in the 1960s and is characterized by its ability to induce vivid hallucinations and altered states of consciousness, even at low doses.
While high doses of psychedelic substances have shown promising results when combined with therapy, they come with risks and require significant resources. An alternative, and increasingly popular yet medically unsanctioned practice, is microdosing – taking very low doses of psychedelic drugs.
Previous studies on microdosing have primarily involved healthy individuals, yielding mixed results. Most did not find significant psychiatric benefits, prompting researchers at the University of Chicago to explore whether individuals with existing depressive symptoms might respond differently to low doses of LSD.
“There has been a great deal of public interest in ‘microdosing,’ or the idea that very low doses of LSD, taken every 3-4 days, can improve mood, cognition and creativity, among many other claims,” explained study author Harriet de Wit, a professor of psychiatry and behavioral neuroscience. “However, such effects are highly susceptible to expectancy effects, i.e., people experience what they expect to experience. Therefore, controlled studies are essential to determine whether the effect of the drug exceeds that of a placebo.”
“Several such controlled studies have been conducted in healthy volunteers, but until now, the effects of the microdoses have been difficult to demonstrate. One limitation of most of the studies to date is that they have tested healthy adults, whereas its effects may be more apparent in participants with some psychiatric symptomatology. This study investigated a low dose of LSD in participants who reported some level of depression.”
The study involved 39 healthy volunteers, aged 18 to 35, who were recruited from the university community. Participants were divided into two groups based on their scores on the Beck Depression Inventory-II, a standard measure of depression. Those with scores indicating mild to moderate depression formed the “high” depression group, while those with lower scores comprised the “low” depression group.
Each participant underwent two five-hour laboratory sessions, receiving either a 26 microgram dose of LSD or a placebo in a random order, with sessions spaced at least a week apart. To ensure a double-blind study, neither the participants nor the researchers knew who received LSD or the placebo during each session. The study included various measures to assess the effects of LSD: subjective mood and drug effects ratings, creativity tasks, emotional facial recognition tasks, cardiovascular measures, and blood tests to measure LSD levels.
Participants, regardless of their depression level, reported feeling the effects of LSD and liked the drug effect more compared to the placebo. The high-depression group showed a tendency to enjoy the effects of LSD more than the low-depression group. Participants with higher depression scores also experienced significant increases in mood measures like elation and vigor following LSD consumption, a trend not observed in the low-depression group.
“We were surprised that the drug preferentially increased feelings of positive mood in the depressed sample, compared to the controls. There are many possible reasons for this, which will need to be examined in future studies,” de Wit told PsyPost.
Perhaps one of the most significant findings of the study was observed 48 hours after the LSD session. Participants in the high depression score group reported a notable decrease in their depression scores, as measured by the Beck Depression Inventory-II, compared to their scores after the placebo session. This suggests a potential lasting antidepressant effect of LSD, particularly in individuals with existing depressive symptoms.
The findings provide preliminary evidence that “people with depressed mood may experience different effects from a single dose of the drug, compared to nondepressed people,” de Wit explained. “However, this initial finding needs to be replicated and extended to other samples.”
Contrary to popular claims about microdosing enhancing creativity, LSD did not significantly alter performance on various creativity-related tasks. Additionally, the drug did not affect emotional facial recognition abilities. In terms of physiological effects, LSD was found to increase both systolic and diastolic blood pressure, while heart rate remained unaffected. Interestingly, the plasma levels of LSD did not correlate with either the subjective experience of the drug or how much participants liked its effects.
However, the study is not without its limitations. The high depression group reported only mild to moderate symptoms, and it’s unclear whether the findings would apply to those with more severe depression. Additionally, the study used only a single dose of LSD, leaving the potential effects of repeated microdosing unexplored. Another limitation was the homogenous nature of the participant pool, primarily consisting of young adults with some prior psychedelic experience and minimal negative reactions.
“The subject sample was small,” de Wit said. “The participants in the ‘depressed’ group reported a relatively low level of symptoms, and so it will be important to see whether this finding is replicable in larger samples including those with more severe symptoms. We do not know why the groups differed: It could have been because of long-lasting neurobiological adaptations (e.g., related to prior stress), or it could be related more directly to their mood state on the day of the drug sessions. We do not know if similar findings would be obtained with other symptomatic samples (e.g., anxiety). We do not know what the effects of repeated administration of the drug would be, in the pattern that people report ‘microdosing’ outside the laboratory.”
Future research should focus on a more diverse demographic, including individuals with a broader range of psychiatric symptoms and past drug use history. It will also be important to investigate whether these findings can be replicated, how long the effects last, and if the results are more pronounced when combined with psychotherapy or in individuals with more severe depression. Further studies should also explore the potential antidepressant effect of even lower doses that do not produce perceptual effects.”
The study, “Greater subjective effects of a low dose of LSD in participants with depressed mood“, was authored by Hanna Molla, Royce Lee, Ilaria Tare, and Harriet de Wit.
