- Chronic administration of serotonin and d-fenfluramine resulted in cardiovascular changes, with serotonin causing ventricular thickening and d-fenfluramine leading to valve regurgitation.
- Microdoses of LSD did not lead to significant cardiac structure or function changes, indicating it may not carry the same cardiovascular risks associated with other serotonergic compounds.
- Differences in the activation duration and intensity of serotonin receptors between LSD and other drugs such as fenfluramine likely explain the lack of cardiac adverse effects in mice treated with low doses of LSD.
Summary of Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
The researchers, Effinger and colleagues, investigate concerns surrounding the burgeoning practice of microdosing psychedelics, specifically focusing on their potential cardiovascular effects. Microdosing involves the regular intake of subhallucinogenic doses of substances like LSD or psilocybin, which many claim can enhance cognitive and emotional well-being. With a notable increase in online searches for microdosing—rising more than thirteenfold from 2015 to 2023, particularly in U.S. states that have decriminalized psychedelics—the long-term health implications are still not well understood. A critical concern that the authors highlight is the role of the serotonin 5-HT2B receptor. Research has shown that prolonged stimulation of this receptor by certain drugs can lead to severe cardiovascular disorders. Notably, fenfluramine, an appetite suppressant, has been linked to significant heart issues, prompting the authors to investigate if chronic microdosing of psychedelics could yield similar problems.Study Approach and Findings
The study involved assessing mice who received various substances, including LSD at low doses representative of microdosing. The researchers employed echocardiography—a heart imaging technique—to monitor any structural or functional cardiac changes over an eight-week period. The microdoses of LSD were established at a fraction of a hallucinogenic dose, intended to produce minimal effects on behavior. Throughout the study, variations in body weight and heart rate were monitored, with no significant adverse effects detected. However, significant changes were observed in mice treated with serotonin, indicating ventricular thickening—a clear signal of potential heart damage. Valvular function evaluations using Doppler echocardiography further illustrated the differences. While d-fenfluramine resulted in observable valve regurgitation consistent with known cardiotoxicity, the LSD groups showed no such effects. The absence of structural or functional heart changes suggests that microdosing LSD does not carry the same risks related to cardiac health.Receptor Activity Assessment
The researchers also delved into receptor-level interactions using advanced assays to quantify the activity of LSD and other compounds at the 5-HT2B receptor. They found that while LSD binds to the receptor effectively, its capacity to activate it was less significant compared to serotonin and norfenfluramine. This reduced efficacy, coupled with the transient nature of receptor activation by LSD, points to why microdosing may not induce the harmful cardiac effects seen with fenfluramine.Implications and Future Directions
Despite the study’s reassuring findings regarding LSD, the authors caution against assuming microdosing is entirely safe, especially for humans. Their research in mice does not necessarily extrapolate to humans, whose cardiovascular responses and drug metabolisms differ. Furthermore, individuals with pre-existing heart conditions could face heightened risks from similar practices. The authors emphasize the critical need for extensive, long-term studies in human participants to truly evaluate the safety of psychedelic microdosing. Overall, this research serves as an initial exploration into the cardiovascular implications of microdosing psychedelics, establishing groundwork for future investigations into the safety and potential risks associated with such practices.See also our coverage of Side Effects of Microdosing Lysergic Acid Diethylamide, and our explainers on side effects. Read the full paper summary on Blossom.
