Are psychedelics the new GLP-1s?
What GLP-1 agonists did for obesity, psychedelic medicine may soon do for mental health.
Have you ever taken SSRIs? I have. They hardly work. So why does everybody take them? (And what are SSRIs, by the way?)
SSRIs are a common class of psychiatric drugs. The acronym stands for selective serotonin reuptake inhibitor. In short, SSRIs block the serotonin transporter, so less serotonin is taken back up into the presynaptic neuron, which increases serotonin activity in other parts of the brain. Serotonin is a neurotransmitter that regulates a slew of functions in the central nervous system. When one neuron sends a serotonin signal to another, most of the serotonin is quickly vacuumed back up by a protein called the serotonin transporter. SSRIs block this protein, so serotonin hangs around for longer in the gap between neurons (the so-called synaptic cleft).
This does two things:
It slightly boosts the strength of serotonin signals.
Over several weeks, it changes how sensitive many brain circuits are to serotonin.
The thing is, A LOT of brain circuits are sensitive to serotonin. We’re talking mood, anxiety, obsessive thoughts, impulse control, sleep, appetite, sexual function, pain, and so much more. Whoever controls serotonin has a pretty good handle on the steering wheel.
How many people take SSRIs? There is no single global headcount, but the available data suggest tens of millions of people all over the world. It’s everywhere. And for many patients, it isn’t working.
SSRIs show small to modest average benefits over placebo, limited remission, and high discontinuation rates. A major 2018 network meta analysis in The Lancet looked at 522 double blind randomized trials of 21 antidepressants, including SSRIs, in 116,477 participants. It found two things:
All antidepressants were statistically more effective than placebo
The average effect size compared with placebo was around 0.3 standard deviations, which is code for “small”, just a few points on common depression scales.
The effect is so little that, according to a peer-reviewed paper published on BMJ Open (Journal Impact Factor of 2.4), “the evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.”
Kirsch 2008, reanalysing FDA data, found “virtually no difference” at moderate depression, and only reached the NICE “clinical significance” threshold (d ≥ 0.5) at the very severe end of the scale.
Fournier 2010 reached a similar conclusion: benefit over placebo increases with baseline severity, and may be minimal or non-existent on average in mild or moderate depression.
Placebo response in depression trials is huge:
Meta analyses of antidepressant RCTs find placebo response rates around 35–40 percent.
Kirsch’s analysis reports that “82% of the drug response was duplicated by placebo.”
Which means that, from a population point of view, most of the improvement people experience after starting an SSRI could have occurred with placebo, time, and supportive care, and only a minority experience a substantial drug specific effect. A 2022 BMJ analysis even suggested that only “about 15% of participants have a substantial antidepressant effect beyond a placebo effect.”
So, the efficacy of SSRIs is still debated, but what about remission rates and drop out data?
The biggest “real world” SSRI trial is STAR*D, where all patients started on citalopram (an SSRI). After the first trial, remission rates were 28–33 percent, response 47 percent. After up to four sequential treatment steps, the original report even claimed a cumulative remission of 67 percent, but with high drop out and method issues. But a 2023 reanalysis that handled missing data more rigorously estimated a true cumulative remission of only 35 percent.
Naturalistic cohorts tell a similar story. One study found about 73 percent of patients discontinued antidepressants within 24 weeks, regardless of which drug they were on.
According to the University of Oxford’s PETRUSHKA project, around 80 percent of people in the UK who are prescribed antidepressants “stop the treatment after just a few weeks.”
TL;DR: For most people, SSRIs mostly do not work, and most people quit early. Why? Because of limited efficacy. And, most importantly, because of annoying side effects.
Nausea, diarrhea, headache, insomnia, dry mouth, tremor, and increased anxiety are all common early on. And sexual dysfunction—that’s a big one. One study found that 73 percent of SSRI users reported sexual side effects, compared with 14 percent on bupropion. Think loss of libido, erectile dysfunction, anorgasmia.
And weight gain, did I tell you about weight gain? Just imagine that in one trial “a significantly higher proportion of paroxetine treated patients (25.5%) gained ≥ 7% in weight compared with the other treatment groups (sertraline, 4.2%; fluoxetine, 6.8%).”
And finally, the bigger of all side effects: sloth. You feel dull: less joy, less sadness—flat like a pancake.
That’s why people stop. And when they do, the troll starts taking its toll. Recent meta analyses of randomized trials suggest about 1 in 6 patients stopping antidepressants have noticeable discontinuation symptoms, and about 2 to 3 percent face severe protracted problems. Typical symptoms include dizziness, flu-like symptoms, insomnia, irritability, anxiety, low mood, strange sensory phenomena. And while for many people this is a few days, for a non-trivial minority, “withdrawal can sometimes be more difficult, with symptoms lasting longer (in some cases several weeks, and occasionally several months)” and “sometimes be severe, particularly if the antidepressant medication is stopped suddenly.”
A bridge to the future
So what do you do when one drug doesn’t work? You add a second one. Atypical antipsychotics like aripiprazole or quetiapine, or old school lithium, are often added on top of an SSRI in so-called augmentation strategies. Meta analyses show that this does increase response and remission rates compared with staying on the antidepressant alone, but the gain is “small to moderate” and comes at a cost: weight gain, metabolic problems, sedation, and so on.
Then came ketamine. At sub anesthetic doses, this old anesthetic blocks NMDA receptors, triggers a rapid glutamate surge and a burst of synaptic plasticity. In layman’s terms, it briefly puts the brain into a “rewiring mode”: all of a sudden, neurons start chatting more and more, forming brand-new connections, making people feel noticeably better within a day. Its S enantiomer, esketamine, was turned into Spravato, an intranasal formulation that turned this effect into a product. Spravato, made by Janssen, the pharmaceutical arm of Johnson & Johnson, was first approved in 2019 for treatment resistant depression (TRD) in combination with an oral antidepressant, then for major depressive disorder (MDD) with acute suicidal ideation or behavior, and more recently as monotherapy in TRD. It has to be given in certified clinics as it can cause sedation, dissociation, spikes in blood pressure and, caveat emptor, “abuse and misuse.” Patients come in, spray the drug, ride out a very strange couple of hours under observation, and a large minority feel noticeably better right from the get-go.
And it’s the real deal. In pivotal trials, adding Spravato to a standard antidepressant led to an additional improvement of about 3.8 to 4.1 points on the Montgomery Asberg Depression Rating Scale (MADRS) at 4 weeks, compared with placebo plus antidepressant, in patients who had already failed at least two SSRIs. Long term open label data show that if you keep giving esketamine weekly, every other week, or every 4 weeks, a big chunk of treatment resistant patients stay in response or remission, with remission rates in this cohort reaching about 46 percent. In a real-world multicenter study of esketamine nasal spray for treatment resistant depression, about two thirds of patients achieved a clinically meaningful response and about 40 percent achieved remission by 3 months, with roughly one third already responding after the first month.
Spravato is now a blockbuster drug tracking a $1.6 billion run rate, which tells you how strong the demand is when something finally moves the needle.
The era of psychedelic medicine
And then came psychedelic medicine. The molecules themselves are not new. LSD was first synthesized in 1938 and by the 1950s psychiatrists were already running hundreds of small studies on LSD for alcoholism and mood disorders before the moral panic of 1960s shut everything down.
The modern reboot started in universities in the 1990s and accelerated through the 2000s and 2010s, with small, tightly controlled trials at places like Johns Hopkins, NYU, and Imperial College. What changed in the last few years is that this moved out of the lab and into Delaware and Bay Street. Around 2019 and 2020 you suddenly had pure play psychedelic medicine companies listing in New York and Toronto, building pipelines around psilocybin, MDMA, DMT, and LSD instead of SSRIs. MindMed, focused on lysergide (LSD) D-tartrate and R(-)-MDMA, was founded in Toronto in 2019 and became the first psychedelic pharmaceutical company to go public on a Canadian exchange, then uplisted to Nasdaq. In London, Compass Pathways, a biotech founded in 2016 that researches psilocybin therapy, became the first psychedelic medicine company to list on Nasdaq in 2020. At the same time, atai Life Sciences, a Berlin based psychedelic platform company, raised hundreds of millions of dollars and went public on Nasdaq in 2021, before combining with Beckley Psytech in 2025 to form AtaiBeckley.
At this point you’re probably wondering, does any of this actually work, or is just New Age mumbo jumbo?
That’s the cool part.
None of it is.
MindMed
MindMed is building around MM120, a lysergide D-tartrate (LSD) orally disintegrating tablet with patent protection out to 2041, and around MM402, an R(-)-MDMA enantiomer in development for autism spectrum disorder (ASD).
The company’s trial of MM120 in generalized anxiety disorder (GAD), published in JAMA in 2025, offered the first solid clinical data on LSD for anxiety. It was a 12-week, multi-center, parallel, randomized, placebo-controlled, double-blind, Phase 2b study designed to assess the dose-response, efficacy, safety, and tolerability of a single dose of MM120 in 198 adults with moderate-to-severe GAD. Participants received a single dose of MM120 (25, 50, 100, or 200 micrograms) or placebo and then were simply followed; there was no protocolized psychotherapy bolted on.
The 100 µg dose of MM120, now being evaluated in three pivotal Phase 3 trials, showed the optimal level of clinical activity in the study. At Week 4, it achieved a 7.6-point greater reduction in HAM-A scores compared to placebo (-21.3 vs. -13.7; p<0.0004; Cohen’s d=0.88) with a 65% clinical response rate and 48% clinical remission rate sustained to Week 12. This all came from a single dose, not from daily pills.
MM120 was generally well-tolerated in this study, with most adverse events rated as mild-to-moderate, transient, occurring on the dosing day, and being consistent with the expected acute effects of the trial drug. Based on these Phase 2b study results and the significant unmet medical need in the treatment of GAD, the U.S. Food & Drug Administration (FDA) has provided Breakthrough Therapy Designation to MM120 for GAD.
Building on positive Phase 2b study results in generalized anxiety disorder (GAD), which showed MM120’s potential antidepressant effects and clinically meaningful improvements on MADRS at the 100 µg dose, the company has gone straight into the Phase 3 Emerge study in major depressive disorder (MDD) using a single 100 µg MM120 ODT dose versus placebo in roughly 140 patients with a 12 week topline readout guided for mid 2026, and is planning a second Phase 3 MDD trial, Ascend, to start in mid 2026 with the same basic 12 week plus 40 week design and 100 µg, 50 µg control or placebo.
In GAD, MM120 is also in two Phase 3 trials, Voyage and Panorama, both built around the same single 100 µg MM120 ODT dose, with enrollment running through 2025 and 12 week topline data guided for 2026, Voyage in the first half of the year and Panorama in the second.
The second MindMed asset, MM402, pushes beyond mood and anxiety into neurodevelopmental conditions. MM402 is the company’s proprietary R(-)-MDMA, the R-enantiomer of MDMA, developed for ASD. Preclinical work in rodent models of ASD suggests that R(-)-MDMA is more potent and enhances social interaction more strongly than racemic MDMA. MindMed has already completed a Phase 1 study in healthy volunteers and plans to initiate a single dose, open label Phase 2a study of MM402 in up to 20 adults with ASD in Q4 2025, targeting core socialization and communication symptoms.
Compass Pathways
Compass Pathways has taken a different route, focusing on one proprietary psilocybin formulation, COMP360, which in 2018 received FDA Breakthrough Therapy designation for psilocybin therapy for TRD.
The anchor data set is the Phase 2b trial in treatment-resistant depression (TRD), published in the New England Journal of Medicine in 2022 and funded by Compass itself. In that study, 233 adults with TRD were randomized to a single 25 mg, 10 mg, or 1 mg session of COMP360, always combined with psychological support. At week 3, the 25 mg group had a 6.6-point greater reduction in MADRS depression scores than the 1 mg control group (a standard “low-dose psilocybin” active placebo), and 36.7 percent met response criteria and 29.1 percent were in remission, compared with 17.7 percent and 7.6 percent in the control arm.
Phase 3 is now confirming that this is not a statistical fluke. In June 2025, Compass reported top-line results from COMP005, the first of its pivotal TRD trials: 258 adults across 32 US sites, a single 25 mg COMP360 session versus placebo, primary endpoint at week 6. The 25 mg arm showed a high statistical significance, clinically meaningful reduction in depression at 6 weeks, and no unexpected safety findings, hitting a 3.6-point advantage on MADRS over placebo and meeting the pre-specified primary endpoint. A second Phase 3 trial (COMP006) with two COMP360 doses and longer follow-up is ongoing, with 9-week Part A data and COMP005 26-week data expected in Q1 2026, and 26-week Part B data from COMP006 expected in early Q3 2026.
Compass is not stopping at unipolar TRD. The same COMP360 platform is being pushed into PTSD, anorexia nervosa, and bipolar II depression. A Phase 2 open-label study in 22 adults with PTSD, run at King’s College London, used a single 25 mg COMP360 dose with structured therapy and followed patients for 12 weeks; published data show consistent improvements in PTSD symptom scores and functioning across that period.
Anorexia nervosa is being tackled through COMP401, Compass Pathways’ Phase 2 proof-of-concept trial of COMP360 psilocybin therapy in adults with anorexia nervosa (25 mg vs 1 mg in about 60 participants across multiple US, UK and Irish sites), built on top of the Phase 1 open-label Nature Medicine feasibility study, which showed that a single 25 mg COMP360 session plus psychological support was feasible, acceptable, and produced clinically meaningful improvements in eating disorder psychopathology at 3 months in 4 out of 10 participants (40 percent), defined as having global Eating Disorder Examination scores within one standard deviation of community normative values.
On top of that, an investigator-initiated open-label study in bipolar II depression, supported by Compass, has already made it into JAMA Psychiatry: a single 25 mg COMP360 session plus psychotherapy in 15 adults with bipolar II depression led to sustained MADRS response and remission in the majority of participants out to 12 weeks.
AtaiBeckley
AtaiBeckley’s strategy is different again: instead of psilocybin or LSD, it focuses on intranasal 5 MeO DMT, DMT, and R-MDMA.
The most visible asset is BPL-003, a proprietary intranasal formulation of mebufotenin benzoate, a synthetic version of 5-MeO-DMT. Sessions are short by psychedelic standards, with the acute experience typically under two hours, and the drug is designed from the start to fit into the same half-day clinic workflow that Spravato pioneered. In 2025, AtaiBeckley reported that their randomized Phase 2b trial in 193 adults with TRD met its primary endpoint and all key secondary endpoints, and BPL-003 demonstrated rapid, robust and durable antidepressant effects with a single dose.
Single 8 mg and 12 mg doses of BPL-003 produced statistically significant and clinically meaningful reductions in depressive symptoms at all study time points versus a 0.3 mg low dose active control, with MADRS scores at day 29 reduced by a mean of 11.1 points for 12 mg and 12.1 points for 8 mg, compared with 5.8 points in the control arm (p = 0.0038 and p = 0.0025, respectively), and improvements detectable as early as one day after dosing and generally maintained through week 8. BPL-003 was generally well tolerated at all doses, with 99 percent of treatment emergent adverse events rated mild or moderate, no drug related serious adverse events or suicide-related safety signals, and the majority of patients considered ready for discharge 90 minutes after dosing.
In light of these results, BPL-003 has already secured FDA Breakthrough Therapy designation for TRD.
The second AtaiBeckley pillar is VLS-01, a proprietary buccal film formulation of DMT for TRD. The idea is to get DMT’s ultra-rapid onset and short duration into a convenient oral transmucosal strip that dissolves on the cheek, again targeting a sub-two-hour clinic stay. Phase 1b data in healthy volunteers have already been reported, and the Phase 2 ELUMINA trial in TRD is underway, randomizing patients to VLS-01 versus placebo buccal film, with topline data to be published in the second half of 2026.
The third leg is EMP-01, a proprietary oral R-MDMA formulation for social anxiety disorder (SAD), developed through the EmpathBio subsidiary, now fully inside AtaiBeckley. In May 2025, Atai announced that the first patient had been dosed in an exploratory phase 2 study of EMP-01 in adults with SAD, with top-line data expected in the first quarter of 2026.
AtaiBeckley also runs an early stage discovery program of novel 5-HT2A agonists, including non-hallucinogenic neuroplastogens, for opioid use disorder and treatment resistant depression. The program applies AI and machine learning guided medicinal chemistry to generate 5-HT2A agonists that are non-hallucinogenic in rodent drug discrimination assays and show antidepressant-like effects in Wistar Kyoto rat models.
So… are psychedelics about to have their GLP-1 moment?
GLP-1 drugs reshaped obesity treatment after decades of stalled innovation. Better yet, they have changed the world and saved who knows how many lives.
Is the same thing about to happen with psychedelics?
Maybe.
If so…
…what happens next?
Disclaimers:
a) At the time of publishing this article, I own shares in Mind Medicine (MindMed) Inc. (MNMD).
b) This article should not be misconstrued as financial or medical advice. Do your own research, talk to experts, and don’t do anything stupid.
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psychedelics are spiritual tools