Depression is a highly prevalent mental health condition. Because many patients fail to respond to standard therapies, there is a pressing need for alternative approaches. Recently, administration of single high doses of psychedelic compounds such as psilocybin and lysergic acid diethylamide (LSD), combined with supportive psychotherapy, have proven effective. Unfortunately, the high doses tested have several drawbacks. For example, older depressed patients complain that the psychedelic experience induced is unpleasant.
Today, an alternative approach is the use of very low doses, or “microdoses” of psychedelic drugs. Anecdotal reports claim that repeated ingestion of LSD microdoses improves depression ratings without producing unpleasant perceptual effects. Several recent placebo-controlled studies have failed to support these beneficial claims.
These negative outcomes may be due to the fact that most of these studies were conducted using healthy adults without significant psychiatric symptoms. A recent study investigated the possibility that microdoses of LSD might produce clinical benefit in individuals with depression at baseline.
The study investigated the effects of a single low dose of LSD (26 µg) or placebo in subjects who scored high (17 or higher) on the Beck Depression Inventory (BDI) as compared to subjects with low, nondepressed, scores (less than 17). The study monitored their mood, cardiovascular, and behavioral responses. Measures of depression were attained during the time the drug was in effect and 48 hours later.
The two groups of subjects, depressed and nondepressed, differed in several ways with their responses to low doses of LSD. The highly depressed patients were not more sensitive to LSD; however, they preferentially were more sensitive to certain aspects of the drug. The depressed patients reported a significantly greater improvement in mood, as measured by reports of vigor and elation.
In addition, patients with greater levels of depression experienced more positive and more stimulant-like subjective effects from LSD. They reported greater psychoactive effects on the 5-Dimensional Altered States of Consciousness measure, including their experience of unity, spiritual experience, blissful state, insightfulness, disembodiment, impaired control/cognition, anxiety, and complex imagery.
When their BDI depression ratings were determined two days after LSD treatment, the depressed patients reported lower depression scores, suggesting that the drug may have a lasting effect on depression. The potential mechanism behind the lasting effects of LSD remains unclear. Animal studies have reported that LSD promotes neuroplasticity in cortical neurons within 24 hours after treatment. Further, these changes have been shown to depend on known chemical mediators of neuroplasticity. (For more about neuroplasticity, read this: The Brain - What Everyone Needs to Know.)
The finding that the more depressed participants reported greater benefits from LSD than nondepressed patients is novel and may offer insights as to why previous studies failed to detect beneficial effects from the drug. The findings suggest that baseline mood and psychiatric symptoms may enhance certain responses to psychedelic therapies.
References
Molla H, et al., (2024) Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacology 49:774 – 781; https://doi.org/10.1038/s41386-023-01772-4
Murphy RJ, et al., (2023) Acute mood-elevating properties of microdosed lysergic acid diethylamide in healthy volunteers: a home-administered randomized controlled trial. Biological Psychiatry, 94:511–21.
LSD May Be More Effective When You’re Already Depressed
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26.03.2024
Depression is a highly prevalent mental health condition. Because many patients fail to respond to standard therapies, there is a pressing need for alternative approaches. Recently, administration of single high doses of psychedelic compounds such as psilocybin and lysergic acid diethylamide (LSD), combined with supportive psychotherapy, have proven effective. Unfortunately, the high doses tested have several drawbacks. For example, older depressed patients complain that the psychedelic experience induced is unpleasant.
Today, an alternative approach is the use of very low doses, or “microdoses” of psychedelic drugs. Anecdotal reports claim that repeated ingestion of LSD microdoses improves depression ratings without producing unpleasant perceptual effects. Several recent placebo-controlled studies have failed to support these beneficial claims.
These negative outcomes may be due to the fact that most........
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