The abysmal psychedelic stock market belies the monumental advancements in psychedelic medicine that have been made within the last two years. It is absolutely clear that psychedelic biotech valuations are completely divorced from fundamentals. Multiple research papers have confirmed then validity of psychedelic-inspired drugs as treatments for mental illnesses on a hard, quantitative level [1, 2]. There are almost 500 ongoing clinical studies of psychedelic substances and psychedelic-assisted therapies (often in combination), and the industry leaders (discussed below) have catapulted multiple drug assets (LSD, ketamine, DMT, psilocybin, and MDMA) into Phase 2 (26 ongoing) and Phase 3 (2 ongoing) clinical trials. Recent regulatory changes in favor of “compassionate use” have already allowed psychedelics to be administered to suffering patients. The industry is fully legitimized and on the cusp of a critical inflection point: regulatory approval of the first psychedelic therapy.
(in collaboration with Numinus)
A Multi-Site Phase 3 Study of MDMA-Assisted Therapy for PTSD (MAPP2)
Completed on 11/17/2022, top-line results not yet available - expected to be published in Q1 2023.
We should expect a New Drug Application from MAPS in 2H23, and if approved this will be the first medical psychedelic commercialized since Sprovato (nasal ketamine) in March 2019, and the first ever psychedelic-assisted therapy for PTSD (an ever growing problem especially among US military veterans). In June 2022, Numinus jumped to the front of the industry with their acquisition of Novamind, which gave them a network of 12 wellness clinics supported by psychedelic-assisted therapy (PAT)-trained clinicians capable of administering MDMA therapy sessions. A successful MDMA approval from MAPS would give Numinus full access to administer MDMA in their treatment clinics; a first of its kind. Once MDMA is validated as a safe and efficacious treatment for PTSD, MAPS will be positioned to quickly pursue other related disease indications.
"The Phase 3 confirmatory results support the development of MDMA-assisted therapy as a potentially new breakthrough therapy to treat individuals with PTSD—a patient population that is often left to suffer for years. Now with two positive Phase 3 trials complete, we can add this important data to the new drug application which we expect to submit in the third quarter of this year."
Read MedicalGold's full coverage of Numinus here.
Phase III, Multicentre, Randomised, Double Blind, Placebo-controlled Study to Investigate the Efficacy, Safety, and Tolerability of a Single Administration of COMP360 in Participants With Treatment-resistant Depression
Recruiting patients, estimated completion date October 2024.
“Our additional analyses underline the robustness of our findings that a single high dose of COMP360 psilocybin, given in conjunction with psychological support, led to a rapid and sustained response for many patients. This phase IIb study was designed to determine the optimal COMP360 dose for our phase III programme, evaluating safety and efficacy at the primary endpoint at week 3. Additionally, we observed consistent improvement in measures of anxiety, positive and negative affect, quality of life, daily functioning, cognition, and self-reported depression. We believe this could make a tremendous difference to patients suffering with treatment-resistant depression, who have few options available to them. Remember, a quarter of the 25mg group maintained response, as measured by the MADRS, at 12 weeks after a single administration with no other antidepressant medication. This finding in itself is unprecedented.”
While Compass is fighting an uphill battle to prove that their psilocybin-based investigational drug, COMP360, can produce a clinically meaningful and sustained response while mitigating treatment-related adverse events, they are the best positioned company to gain approval for the first psilocybin therapy for patients suffering from treatment-resistant depression (TRD). TRD is especially pernicious because it remains impervious to existing anti-depressants, and patients are at increased risk for comorbid anxiety disorder, higher suicide risk, as well as deleterious metabolic changes . A steep hill to climb indeed, but Compass appears confident that their Phase 2b data is encouraging enough to launch a 2-trial pivotal Phase 3 program [Link]. Once approved for TRD, Compass may decide to pursue additional clinical trials for major depressive disorder (MDD), which will likely show positive results since MDD is a less severe form of depression than TRD. Alternatively, COMP360 may be prescribed off-label for MDD at physcians' discretion.
A Phase 2, Multi-center, Randomized, Double-Blind, Parallel-Group, Dose-Finding Study to Assess the Effect of Four Doses of MM-120 (LSD D-Tartrate) for the Treatment of Anxiety Symptoms
First patient dosed on August 25, 2022.
MindMed stands to commercialize the first LSD pharmaceutical since Delysid lost its patent in the 1960's. This will legitimize the use of Indolealkylamines, which include psilocybin and DMT in addition to LSD, and are based on the core serotonin structure.
Read MedicalGold's full coverage of MindMed.
A Double-blind, Randomised, Placebo-controlled Study of Intravenous Doses of SPL026 (DMT Fumarate), a Serotonergic Psychedelic, in Healthy Subjects (Part A) and Patients With Major Depressive Disorder (Part B)
Completed on 12/22/2022, and top-line data released on 1/25/2023 (summary of the results below).
Updated open-label results 3/7/2023 - Further analysis of the Phase IIa dataset is ongoing and full trial results will be submitted for publication in a peer-reviewed journal.
This is the first placebo-controlled efficacy study completed to date that investigates a short-duration psychedelic for depression and demonstrates both a rapid (effects seen at 1 week) and durable response (effects endured up to 12 weeks). The change in MADRS score for depression is astonishingly high, more than double that of COMP360 (psilocybin) in Compass Pathway's DMT for treatment-resistant depression (TRD) trial (not to draw a direct head-to-head comparison between the two studies, as TRD is a completely different beast compared to major depressive disorder and much less tractable).
We are pleased that a significant number of patients benefited from the treatment in our trial. SPL026 with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable, with a remission rate of 57% at three months following a single dose of SPL026. It was encouraging to see that SPL026 demonstrated a favourable safety and tolerability profile in MDD patients in this study, consistent with our Phase I study. The results are clinically meaningful and enable us to progress into an international multi-site Phase IIb study where we seek to further explore the efficacy and safety profile of SPL026 in a larger MDD patient population.”
A Phase 2a Safety and Feasibility Study Evaluating Psilocybin (TRP-8802) Administration in Concert With Psychotherapy in the Treatment of Binge Eating Disorder
Ongoing, interim results of first 5 patients announced on 1/5/2023 (see data below).
These results affirm that binge eating disorder (BED) is a viable target for psychedelic-assisted psychotherapy using a psilocybin/psilocin analog. Tryp's proprietary IV formulation of psilocin, TRP-8803, is positioned to be the first psychedelic pharmaceutical that overcomes the limitations of oral psilocybin by reducing the time to onset and controlling the duration of the experience.
"The magnitude and consistency of the trends observed in this interim analysis are incredibly encouraging. Furthermore, these preliminary results provide us with the confidence that BED is a viable target for future studies with psychedelic-assisted psychotherapy utilizing TRP-8803, our proprietary IV formulation of psilocin that alleviates numerous shortcomings of oral psilocybin including: significantly reducing the time to onset of the psychedelic state, controlling the depth and duration of the psychedelic experience, and reducing the overall duration of the intervention to a commercially feasible timeframe. Our strategy is to perform small exploratory studies using TRP-8802 for unique indications including BED, fibromyalgia and irritable bowel syndrome, all in partnership with leading academic institutions. Once a positive clinical signal is identified in studies using TRP-8802, we intend to perform subsequent studies with TRP-8803."
These late-stage clinical trials present unequivocal evidence that psychedelic-inspired pharmaceuticals have potent efficacy against a wide range of mental ailments, and will be the next revolution in psychiatric treatment. We are witnessing an arms race of sorts, wherein multiple companies are developing similar technologies against a relatively small set of overlapping disease indications. This is not an unprecedented phenomenon (just look at the cancer immunotherapy space and PD-1 inhibitors), and it is truly a great sign for the entire industry as more attention and capital flows into the sector seeking a competitive edge. The first approval of a DMT, psilocybin, or LSD-based compound will herald a new age of enlightenment for mental health practitioners and their suffering patients, opening the floodgates of R&D and igniting the smoldering capital markets.
While these industry leaders pave the way, there are many smaller psychedelic biotechs that will benefit from the tailwinds created by their big brothers.
Stay tuned for MedicalGold's "Top 5 Early-Stage Clinical Trials To Watch In 2023".
 Daws, R.E., Timmermann, C., Giribaldi, B. et al. Increased global integration in the brain after psilocybin therapy for depression. Nat Med28, 844–851 (2022). https://doi.org/10.1038/s41591-022-01744-z [Link]
 Davis AK, Barrett FS, May DG, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021;78(5):481–489. doi:10.1001/jamapsychiatry.2020.3285 [Link]
 Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med27, 1025–1033 (2021). https://doi.org/10.1038/s41591-021-01336-3 [Link]
 Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., Bird, C., Blom, R. E., Brennan, C., Brusch, D., Burke, L., Campbell-Coker, K., Carhart-Harris, R., Cattell, J., Daniel, A., DeBattista, C., Dunlop, B. W., Eisen, K., Feifel, D., … Malievskaia, E. (2022). Single-dose psilocybin for a treatment-resistant episode of Major Depression. New England Journal of Medicine, 387(18), 1637–1648. https://doi.org/10.1056/nejmoa2206443 [Link]
 Jaffe, D.H., Rive, B. & Denee, T.R. The humanistic and economic burden of treatment-resistant depression in Europe: a cross-sectional study. BMC Psychiatry19, 247 (2019). https://doi.org/10.1186/s12888-019-2222-4 [Link]
 Turkoz, I., Alphs, L., Singh, J., Jamieson, C., Daly, E., Shawi, M., Sheehan, J. J., Trivedi, M. H., & Rush, A. J. (2021). Clinically meaningful changes on depressive symptom measures and patient‐reported outcomes in patients with treatment‐resistant depression. Acta Psychiatrica Scandinavica, 143(3), 253–263. https://doi.org/10.1111/acps.13260 [Link]
 Holze F, Gasser P, Müller F, Dolder PC, Liechti ME; (n.d.). Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness: A randomized, double-blind, placebo-controlled phase II study. Biological psychiatry. Retrieved January 26, 2023, from https://pubmed.ncbi.nlm.nih.gov/36266118/ [Link]
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