A Look at MindMed’s phase 2a trial using low doses of LSD for ADHD
ADHD (aka Attention Deficit Hyperactivity Disorder) affects around 360 million adults worldwide, and is managed with medications that are ineffective in 30% of patients. In late 2021, MindMed announced the initiation of a phase 2 clinical trial where LSD will be administered to individuals affected by ADHD. How could psychedelics, so far only associated with mood disorders like anxiety and depression, represent a therapeutic option for the management of ADHD?
First, a bit about the condition itself. ADHD is a mental disorder where individuals show agitated, often impulsive and hyperactive behaviours, making it hard for them to concentrate, and can also bring about mood disorders like anxiety. Although the actual causes are still unknown, potential candidates include dysfunctional production of certain neurotransmitters like norepinephrine and dopamine, and studies suggest interactions between the genetics of an individual and their environment could play a role in the development of the condition.
This can be recognised during childhood, but it is also diagnosed for the first time in adults, and it is usually treated with cognitive behavioural therapy (CBT) or medications like the stimulants Adderall and Ritalin, which target norepinephrine and dopamine, neurotransmitters also implicated in clinical depression, and non-stimulants like Strattera and Kapvay. The stimulants have a much faster onset than the non-stimulants (instants vs weeks), but neither of them lasts for more than 24 hours and thus needs to be taken once (stimulants) or twice a day (non-stimulants). Quite a medical commitment for the patients, given the costs and considering that they are not effective or bring adverse effects on 30% of patients.
The phase 2a clinical trial initiated by MindMed is in collaboration with the University Hospital Basel and Maastricht University, and is designed to examine the effect of low doses of LSD on ADHD patients. There is scarce amounts of research available on the topic, but the jump into clinical trials was prompted by the known benefits of psychedelics to conditions co-occurring with ADHD, like anxiety. In addition, some studies suggest that cognitive benefits derive from microdosing psychedelics, such as enhanced concentration and focus, something that affects ADHD patients.
Therefore, it is believed that these substances could be used as safer and more effective alternatives to stimulants, which can sometimes trigger addiction. Again, the evidence for this theory is still quite limited, including so far patients’ personal accounts, such as the comedian Deborah Frances-White, an ADHD patient who reported benefits from a psychedelic retreat in this article, as well as other anecdotes in online surveys.
The data from these surveys could offer an interesting insight, as in population of microdosers ADHD was found to be the third most frequent condition reported. Even pioneers in the field of psychedelic research, like Albert Hoffman (the creator of LSD) and James Fadiman, sustain that small doses of psychedelics make a healthier alternative to certain currently used medications for ADHD.
Hence the double-blind, placebo-controlled phase 2a trial by MindMed is now recruiting patients, aimed at “evaluating the therapeutic utility of repeated low doses of LSD”. LSD, in particular, was chosen among all psychedelics as multiple studies support its potential to improve certain cognitive processes. Moreover, administrating it in microdoses makes it safe and tolerated by patients, as previous studies have shown.
Here, 20 micrograms of LSD will be administered to around 50 patients twice a week for 6 weeks, with the same dose schedule applied to the group receiving the placebo. A rating scale will be used to assess any changes in ADHD symptoms (the “ADHD-RS”), which mainly measures hyperactivity, impulsiveness and distraction.
As for all medical conditions, finding an alternative which is more effective, cheaper, and with minimal or no adverse effects would be ground-breaking for ADHD therapeutics. We will follow this trial closely and see if LSD indeed offers this kind of hope.