In order for psychedelic medicines to be legalized in a doctor-prescribed therapy setting, they must first pass through the three phases of the clinical trial system. In this article, we’ll take a brief look at the top psychedelic clinical trials pushing psychedelic medicines toward legalization. Of course, each trial is placebo-controlled and double-blinded.
MDMA Therapy for PTSD
Arguably the most exciting of the top psychedelic trials on this list, the nonprofit MAPS is currently sponsoring its second Phase 3 clinical trial, attempting to treat PTSD with MDMA-assisted therapy. If this trial is as successful as the first — where 88% of patients saw their symptoms decrease by 50% or more and 67% improved so much they “no longer qualified for a PTSD diagnosis” — then MDMA therapy for PTSD could be legalized as early as the end of next year.
This Phase 3 trial has 100 participants — half of whom are in the placebo group. Those who receive MDMA will undergo 3 MDMA-assisted therapy sessions over the course of 12 weeks, where they will receive either 80 or 120 mg of MDMA, followed by a supplemental half dose 1.5-2 hours later. Each MDMA session will be followed by three integration sessions in the following week.
This trial, entitled MAPP2, is expected to wrap up in November 2022.
Psilocybin Therapy for Treatment-Resistant Depression
Compass Pathways (Nasdaq: CMPS) is set to launch not one, but two separate Phase 3 trials attempting to treat Treatment-Resistant Depression (TRD) with psilocybin-assisted therapy, using a proprietary synthetic version of psilocybin called Comp360. The first patients should be dosed by the end of 2022.
The first trial, named COMP005, will have 378 participants, two-thirds of whom will receive one dose of 25 mg of psilocybin (considered a large dose) paired with therapy. The other third will receive a placebo and therapy. We should expect the results of this trial by the end of 2024.
The second trial, named COMP006, will have 568 patients, and will test two administrations of psilocybin in each participant, with patients receiving doses of 25 mg of psilocybin, 10 mg, or the placebo (1 mg). We should expect the results of this trial in 2025.
These trials will be closely watched to see if their results are better than those found in Compass’ Phase 2b trial. While it was considered a success, the results were not game-changing. In that trial — where patients received one 25 mg dose of psilocybin paired with therapy — only 24.1% of patients saw a 50% or greater decrease in their symptoms 12 weeks after treatment. Furthermore, 83.5% of patients had adverse events, though only 6.3% of patients (5 people) had an “emergency” adverse event.
Therefore, it will be interesting to see if the number of adverse events can be reduced by small tweaks to the procedure and whether a second dose of psilocybin will increase the likelihood of patients receiving benefits from the trial.
LSD to Treat Generalized Anxiety Disorder
In August, MindMed (Nasdaq: MNMD, NEO: MMED) dosed the first patient in a Phase 2b trial attempting to treat Generalized Anxiety Disorder with MM-120, MindMed’s LSD. Interestingly, unlike all other trials in this article, MindMed is measuring whether the medicine of LSD itself is effective in reducing anxiety symptoms, as opposed to the psychedelic combined with therapy.
This trial has 200 patients who will receive either the placebo or a single LSD dose, ranging from 25 micrograms (a small dose) to 200 micrograms (a large dose). The main purpose of this trial is to determine which dose level is the most effective in reducing anxiety symptoms, which will be measured four weeks after LSD administration, and then again 12 weeks after. Of course, safety and tolerability will also be measured.
This trial follows MindMed’s Phase 2 trial that used 200 micrograms of LSD to treat anxiety disorders, which saw 65% of patients see a reduction in their symptoms of at least 30%. These were very positive results, so hopefully their Phase 2b trial will replicate them, or perhaps even improve upon them.
The current study is expected to finish by the end of 2023.
DMT Therapy to Treat Major Depressive Disorder
Dosing has been completed in Small Pharma’s (TSXV: DMT, OTCQB: DMTTF) Phase 2a trial treating Major Depressive Disorder (MDD) with DMT-assisted therapy. The company used its intravenous formulation of DMT, called SPL026.
This trial used a single dose of DMT or the placebo, and the reduction of depression levels (using the MADRS scale) will be measured two weeks after administration, and then again 12 weeks after dosing.
This trial is the world’s first Phase 2a DMT clinical trial, so many will be watching the results with bated breath. DMT causes similar — if more intense — effects as psilocybin, a molecule it is chemically related to. While psilocybin’s effects can last between 6-8 hours, DMT’s effects wear off within half an hour. If the two medicines are equally effective in treating depression, then DMT would by far be the more cost-effective medicine, as therapists and support staff would not have to be paid a full day’s work for each patient.
Preliminary results of this trial are expected in early 2023.
A Shorter-Acting, Next-Generation Psilocybin to Treat Major Depressive Disorder
In August, Cybin (NEO:CYBN, NYSE American:CYBN) dosed the first patient in their Phase 1/2a trial, attempting to treat MDD, with their next-generation psilocybin, named CYB-003. Cybin says that preclinical trial results show that CYB-003 is shorter-acting, safer and has more consistent effects among patients than traditional psilocybin.
This trial is important as it is one of the first next-generation psychedelics in clinical trials. While classical psychedelics have shown great promise in treating mental health conditions such as depression, they are not perfect in a clinical setting. In particular, the long duration of effect of medicines such as psilocybin can make treatments prohibitively expensive for many. If the current clinical trial can back up Cybin’s claims regarding CYB-003, it could jump to the top of the list of promising psychedelic medicines. But of course, we will have to wait to see the data.
The trial will have 40 patients, who will each receive two doses of CYB-003, paired with therapy. After each dose and integration session, the change in depression scores will be measured with the MADRS scale.
The trial’s end date is currently set as July 2023.