In a significant development for mental health treatment, MindMed Inc. has announced that its LSD formulation, MM120, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of Generalized Anxiety Disorder (GAD). This designation follows encouraging results from a clinical trial demonstrating the drug's potential to provide significant and lasting relief from anxiety symptoms.
The biopharmaceutical company's trial included 198 participants and was designed to evaluate the safety, dosing, and effectiveness of MM120 in managing anxiety symptoms. Some patients experienced significant anxiety reduction and relief lasting weeks after a single dose, leading to the Breakthrough Therapy designation. The FDA's decision allows MindMed to proceed more quickly through the drug-approval process, recognizing the agent's potential to solve a serious problem.
Clinical Trial Results
According to MindMed’s Chief Medical Officer Dan Karlin, M.D., "The clinical improvement for many patients was more than double what we see with today’s standard of care. This occurred at all levels of anxiety, from moderate all the way up to severe." The multicenter, randomized, double-blinded trial tested doses of 25, 50, 100, and 200 micrograms of LSD compared with a placebo.
The current standard of care for GAD typically involves a combination of cognitive behavioral therapy and medication. However, medications often require time to take effect, and finding the right dosage can involve experimentation. In contrast, a single dose of MM120 in clinical trials appeared to be significantly more effective.
Purity and Safety
One key difference between MM120 and illicitly obtained LSD is its purity. "LSD is difficult to manufacture with high purity and tends to degrade quickly in the presence of light and water," Karlin explained. "We’re manufacturing it to pharmaceutical industry standards, a highly pure version that is also shelf-stable." Most adverse effects reported in the study were mild to moderate, occurring primarily on the day of the study. These included euphoric feelings, illusions and hallucinations, anxiety, abnormal thinking, headaches, dizziness, nausea, excessive sweating, vomiting, numbness or tingling of the skin, and pupil dilation.
Future Directions
A larger Phase 3 clinical trial is scheduled to begin in late 2024 to gather additional data on MM120’s therapeutic effects. MindMed’s psychedelic protocols are distinguished by the use of safety monitors rather than clinical therapists, as a way to test whether the benefit of anxiety relief stems directly from the drug itself or from the therapist. The pharmacologic effects of LSD last up to 12 hours, and careful monitoring is part of the FDA guidance.
Recreational Use and Risks
Recreational use of LSD carries multiple medical and psychiatric risks, particularly with frequent or high doses. LSD can trigger or exacerbate underlying psychiatric disorders, leading to psychosis, schizophrenia, or long-term hallucinations. Uncontrollable visual disturbances can occur even after the drug has worn off. Bad trips, or intense, negative LSD experiences, may prompt emergency room visits, calls to poison center hotlines, acute anxiety, paranoia, and even panic attacks requiring medical intervention. Flashbacks also pose an important risk. Unexpected re-experiences of an LSD trip long after the drug’s effects have faded, flashbacks can occur unpredictably days, weeks, or even years later. Altered perceptions caused by LSD can impair a person’s sense of reality, leading to self-harm or accidents, especially in unsafe environments. LSD may also increase blood pressure and heart rate, posing risks for individuals with preexisting heart conditions or hypertension. Severe dehydration and hyperthermia have been reported when LSD causes users to lose touch with bodily needs, like hydration, particularly at festivals or other events. Combining LSD with other drugs that increase serotonin levels, such as MDMA (ecstasy), may lead to serotonin syndrome, a potentially life-threatening condition caused by excessively high levels of serotonin in the blood.
Current Status
Today, LSD is viewed by many researchers and some regulatory bodies as a potential tool in the mental health treatment arsenal. While still classified as a Schedule I drug, there is a push to re-evaluate LSD’s status and expand research access. Early LSD data for generalized anxiety disorder (GAD) is promising. Also, with the approval of the ketamine-related medication Spravato for treatment-resistant depression, an FDA roadmap for hallucinogenic approval with safety monitoring already exists. The future of LSD as a medication depends on Phase-3 clinical trials and their outcomes, as well as on changing attitudes towards psychedelics in the medical and public domains. In the meantime, recreational use likely will increase, and, sadly, so too will reports of dangerous outcomes.
