This article was written by Anne-Sophie Geldmeyer, a summer research intern, based on Molla, H, R Lee, I Tare, H de Wit (2023) Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacology 49(5):774-781
Around 8% of people in the US struggle with depression, and some individuals don’t respond to traditional anti-depressants. Recently, a growing trend called “micro-dosing” has emerged as a potential alternative. This involves taking about one-tenth of a standard hallucinogenic dose of a substance like Lysergic Acid Diethylamide (LSD) every three to four days. While many people report that the drug improves mood and cognitive function, these claims are mostly anecdotal, that is, they have not been tested under blinded controlled conditions. The few studies that have examined LSD micro-dosing in healthy adults have shown no clear evidence of mood-enhancing effects.
However, a recent study conducted at the HBPL might change the conversation. This study is among the first to report that low-dose LSD may differentially affect people with depression. Thirty-nine participants completed two sessions and received either an inactive placebo or a single dose of 26 micrograms LSD, under double blind conditions. Half of the participants scored high on a depression scale at intake. During the sessions, changes in mood were monitored and 48 hours after the sessions, participants completed the depression questionnaire again. Unlike past research, this study found that a low dose of LSD had different effects in depressed individuals compared to healthy volunteers. It enhanced psychedelic effects and decreased depression in moderately depressed people.
In the current study, moderately depressed people reported feeling more spiritual, stimulated, and overall felt more positive psychedelic effects than healthy people after taking a low dose of LSD. This suggests that LSD might have a different effect on people with existing psychiatric conditions and it may explain why previous research has been inconclusive – previous studies only examined the effects of LSD on healthy adults. In addition to a greater psychedelic effect, depressed individuals experienced less anger, an increase in positive mood, and a decrease in depression two days after their LSD session, compared to no significant changes for the non-depressed individuals. These findings raise the possibility that low doses of LSD may be effective as a new psychiatric treatment for depression, especially for people who do not respond to traditional anti-depressants.
So, how does LSD potentially help with depression? It is hypothesized that LSD and depression act on similar neural systems in the brain. Depression decreases activity in certain cortical regions while LSD promotes neuroplasticity in those same regions. Neuroplasticity is the brain's ability to form new neural connections. This may also explain why healthy individuals, with a healthy baseline cortical brain volume, experience less of an effect: the neuroplasticity that LSD induces is not as great because they have more brain volume to begin with.
Although this study is one of the first to conclude an effect of LSD on depressive symptoms, these results support a larger consensus that psychedelics can be a new alternative for mental health treatments. While traditional antidepressants often take months to kick in, LSD induces lasting effects within two days of taking it. Often, a micro-dose is so low (less than 26 micrograms), that the individual doesn’t experience immediate subjective effects such as sensory distortion or changes in mood. This allows micro-dosing LSD to be comparable to traditional dosing of anti-depressants.
While this study is a promising step forward, many questions remain unanswered. For instance, how do psychedelics, such as LSD, impact people with more severe depression? What is the effect of higher or more frequent doses? Could the enhanced psychedelic experience be crucial to reducing depression? And would low-dose LSD in conjunction with therapy be more effective?
It is exciting to see the field of psychedelic research evolve, and we hope to answer these questions soon. The results of this study allow us to envision a future where mental health treatment is more innovative, timely, and accessible, especially for people who don’t respond to traditional therapies.