It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Scientists have demonstrated, for the first time, that several psychedelic drugs – including psilocybin, LSD, mescaline, DMT and ayahuasca – produce a common pattern of brain activity despite their distinct chemistries.
An international consortium led by a McGill University researcher pooled brain imaging data from labs across five countries, creating the largest study of its kind to date.
The findings, published in Nature Medicine, could help guide the design of future treatments for mental health disorders.
“This is a breakthrough in how we think about psychedelic drugs,” said senior author Danilo Bzdok, Associate Professor in McGill’s Department of Biomedical Engineering and Canada CIFAR Artificial Intelligence Chair at Mila. “For the first time, we show there’s a common denominator among drugs that we currently consider completely separate.”
Two measurable changes in the brain
While different psychedelics have shown benefits for some mental health conditions, how they produce similar effects despite their chemical differences remains a mystery. The meta-analysis identified two consistent neural effects across five of the most common drugs.
Normally, each brain system communicates strongly within itself, maintaining tight, organized networks. The researchers found that under the influence of psychedelics, these connections weaken, making the networks less rigidly structured.
The second neural effect is that psychedelics increase communication between different brain networks, allowing signals to cross boundaries that are usually separate. This “cross-talk” may help explain the hallucinations and other unusual thoughts, sensations and perceptions people report during psychedelic experiences.
An ‘X-ray’ of global psychedelic research
The meta-analysis combined results from 11 datasets, analyzing more than 500 brain imaging sessions from 267 participants.
Psychedelic neuroscience studies are typically small, often limited to 10 to 30 participants because of high costs and strict regulations. Studying five different psychedelics in a single experiment would be nearly impossible, the authors note.
“This approach gives us an X-ray view of the entire research community,” said Bzdok.
The thawing of ‘psychedelic research winter’
Interest in psychedelics for mental health treatment has surged in recent years, fuelled in part by advances in brain imaging technologies. The revival follows what authors call the “psychedelic research winter” of the 1970s, when studies were limited by criminalization and associations with counterculture.
“Many drug therapies for depression, for example, have changed little over the past decades. Psychedelics may represent the most promising shift in mental health treatment since the 1980s,” said Bzdok.
He added that, as researchers in this emerging field still face logistical hurdles, the results provide a yardstick against which future studies can be measured and may help move the needle toward loosening strict regulations.
About the study
“An international mega-analysis of psychedelic drug effects on brain circuit function” by Manesh Girnand Danilo Bzdoket al., was published in Nature Medicine.
Psychedelic-assisted therapy may be no more effective than traditional antidepressants when patients know what drugs they are actually taking, according to a first-of-its kind analysis that compared how well each type of drug worked for major depression.
Psychedelic-assisted therapy has resisted placebo-controlled testing methods — the gold standard in clinical trial design. Due to their powerful subjective effects, nearly everyone in the trial knows whether they received a psychedelic or the placebo even if they are not told.
But in trials of antidepressants, participants may not figure out whether they have received the drug or a placebo, which makes it hard to compare them with psychedelics.
To get around this problem, researchers from UC San Francisco, UCLA, and Imperial College, London tried a different approach. They compared the results from psychedelic therapy trials to the results from so-called open-label trials of traditional antidepressants, in which the participants all knew they were getting an antidepressant. That way, both treatments benefitted equally from the positive effect of patients knowing that they were being given a drug instead of a placebo.
The findings both surprised and disappointed them: there was virtually no difference.
“Unblinding is the defining methodological problem of psychedelic trials. What I wanted to show is that even if you compare psychedelics to open-label antidepressants, psychedelics are still much better,” said Balázs Szigeti, PhD, a clinical data scientist at UCSF’s Translational Psychedelic Research Program, who led the study. “Unfortunately, what we got is the opposite result — that they are the same, which is very surprising given the enthusiasm around psychedelics and mental health.”
Szigeti is the co-first author of the paper with Zachary J. Williams, MD, PhD, of UCLA; Hannah Barnett, MSc, of Imperial College, London is also an author. The study appeared March 18 in JAMA Psychiatry.
A sobering view
The hype around the use of psychedelics like psilocybin, or “magic mushrooms,” and LSD, to treat such conditions as depression and addiction has grown in recent years as an increasing number of studies have shown promising results, particularly for people who haven’t responded to traditional antidepressants.
The new findings don’t mean that psychedelic therapy does not work — just that it does not work better than traditional antidepressants. Patients improved substantially from both types of treatments, reducing depression scores by about 12 points on a standard scale.
Part of what has made psychedelics seem impressive in trials than antidepressants is how much more those who received the psilocybin or LSD improved than those who did not get it.
But the researchers concluded that this was the result of the lack of blinding in psychedelic trials: those who got the drug improved more because they knew they had gotten it, while those who received a placebo did worse because they knew they did not. Whereas in trials of traditional antidepressants, the difference between the groups was much smaller, making it seem like the drugs weren’t that effective.
When this ‘knowing the treatment’ factor leveled out, the seeming advantage of psychedelics disappeared.
“Psychedelics may still be a valuable treatment option,” Szigeti said. “But if we want to understand their true benefits, we have to compare them fairly — and when we do that, the advantage over standard antidepressants is much smaller than many people, including myself, expected.”
Funding: None.
Disclosures: Williams received consulting fees from Roche. The other authors did not declare any conflicts.
Journal
JAMA Psychiatry
Thursday, March 19, 2026
The scientist who warned that profit, not science, decides which drugs reach patients
Dr. Gabriella Gobbi, CINP president-elect and McGill neuropsychopharmacologist and psychiatrist, challenges the logic of drug discovery
MONTREAL, Quebec, CANADA, 17 March 2026 – Dr. Gabriella Gobbi, Professor of Psychiatry at McGill University, Canada Research Chair (Tier 1) in Therapeutics for Mental Health, Staff Psychiatrist at the McGill University Health Center (MUHC), and Senior Scientist, Brain Repair and Integrative Neuroscience Programat the Research Institute of the MUHC, and President-Elect of the Collegium Internationale of Neuropsychopharmacology (CINP), has issued an unambiguous challenge to the global drug-development system, warning that promising treatments for mental illness are failing to reach patients not because the science is flawed but because venture capital and profit motive govern which compounds advance through clinical trials. Her warning appears in a new Genomic Press Interview published in Brain Medicine.
"My greatest fear concerns the future of psychopharmacology and drug discovery," Dr. Gobbi states in the interview, "not because the science is failing, but because a greedy system oversees innovation today." She describes a landscape in which public funding can sustain early academic research, but the more expensive steps, from toxicology to first-in-human trials, depend on private investment that is guided by margin expectations rather than medical need. "We may lose good, non-expensive treatments because a greedy, capitalistic system controls which drug will finally be brought to market."
A Career Built on Bedside Questions
Dr. Gobbi grew up in a book-filled house in central Italy, the granddaughter of a man who died under Allied bombing in March 1945 after writing from a German prison to insist that his children receive the education he himself had been denied. That inheritance, part moral conviction and part intellectual hunger, runs as a thread through everything she has since done. At fourteen she put down comic books and picked up Freud. In high school she read about Rita Levi-Montalcini and the discovery of nerve growth factor, and understood that the brain was not fixed but plastic, a revelation that pointed her toward medicine. By twenty, during training in Rome, she had encountered translational research, the practice of moving continuously between laboratory bench and clinical ward, and found that she could not relinquish either world.
The path to independence was neither smooth nor linear. In Italy during the 1990s, academic positions were controlled by senior professors acting as gatekeepers, and Dr. Gobbi spent time working at a private psychiatric hospital in a small central-Italian town, applying to PhD programs and genuinely unsure whether she would ever gain entry to research. The turning point arrived on the evening of January 29, 1996, in the form of a telephone call. She was invited to sit a PhD entrance examination in Cagliari, in Sardinia, the following morning. She boarded a plane at eleven that night. At eight the next morning she sat the exam, and she won. That examination opened the door to work with Professor Gianluigi Gessa, a neuroscientist known for landmark contributions to the neurobiology of dopamine and addiction. Two years later, at a Biological Psychiatry meeting in Nice, a chance conversation with Professor Pierre Blier led to an invitation to join his laboratory at McGill. That single year in Montreal became more than two decades.
From Cannabis and Anhedonia to Melatonin and Psychedelics
The clinical observation that drives her best-known research line is almost painfully simple. In the early 2000s, she kept seeing adolescents and young adults who smoked cannabis and who, in the years that followed, developed depression marked by profound anhedonia. The bedside pattern became a bench question. In 2007 her laboratory reported one of the first links between cannabinoids, serotonin systems, and depression-related phenotypes. In 2010, animal-model studies demonstrated that adolescent cannabis exposure could increase vulnerability to later depressive-like outcomes. By 2019, supporting evidence had emerged in human cohorts. This body of work has now accumulated more than 1,700 citations and contributed directly to public-health decisions in Quebec. Dr. Gobbi also testified as an expert witness before the Canadian Senate and the Ministries of Health and Justice in Quebec on cannabis policy, contributing to legislation raising the legal age for cannabis access and to the regulation of cannabis advertising.
A second major research program, running in parallel since 2006, has focused on the melatonin MT2 receptor, a target that was poorly understood when her group began. Her laboratory contributed to defining MT2 receptor localization and elucidated its specific role in restorative NREM sleep and neuropathic pain. An MT2-selective partial agonist, a first-in-class candidate, is now moving from early discovery toward clinical development. "I have learned that in science, the projects that take the longest are often those that yield the most meaningful results," she observes in the interview. Her laboratory began investigating psychedelics in 2013, before the contemporary wave of clinical trials brought the field to prominence, characterizing the anxiolytic and prosocial effects of LSD in preclinical models and beginning to identify underlying molecular mechanisms including mTORC1 signaling. That work is now extending to psilocybin, DMT, and 5-MeO-DMT, while new clinical studies aim to identify objective neurophysiological biomarkers of psychedelic action in humans.
The Hidden Tax on Women in Science
Dr. Gobbi does not confine her scrutiny to drug-development economics. She speaks with notable directness about gender inequality in academic science, describing both overt harassment and a quieter structural erosion: unequal access to administrative support, diversion toward low-visibility service work, and a conference-invitation culture that disadvantages researchers who carry disproportionate caregiving burdens. "This is the cause that fires me up the most," she states, "changing the structure of our scientific culture so excellence is recognized without imposing an additional, hidden tax on women." In her current role as President-Elect of the CINP, the organization whose presidency she will hold as its first woman in the organization's 70-year history, she has heard such accounts repeatedly from accomplished women who have been isolated, evaluated inconsistently, or simply not invited to the table.
The Letter and the Paddleboard
There is a letter from Dr. Gobbi's mother, written before her death from glioblastoma in 2000, that she names as her most treasured possession. It is the kind of detail that resists elaboration, so this account will leave it alone. What she says about happiness is perhaps more useful to science journalism: her happiest moments have occurred in those rare instants in research when data suddenly align and something obscure becomes clear, "the feeling that nature has briefly lifted a corner of the veil, and that an experiment is no longer just results on a page but a story that finally makes sense." When she disconnects entirely, in summer, she paddles on the Adriatic Sea. In Quebec she skis in spring, when the light softens. Winter skiing here, she notes in the interview, is simply too cold.
Asked what she would change about herself, Dr. Gobbi does not cite a scientific limitation. She wishes she had sought mentorship and leadership education earlier. She began her career as an assistant professor without a mentor and without foundational training in management, grant-writing, or conflict resolution. The regret is characteristic: it is not personal but structural, a comment about what academic systems fail to provide rather than about what she personally lacks. Her life philosophy, offered at the interview's close, is unadorned: "Do your best, stay true to what matters, and trust what comes."
Dr. Gabriella Gobbi's Genomic Press interview is part of a larger series called Innovators and Ideas that highlights the people behind today's most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist's impact on the field, while also touching on broader human themes. More information on the research leaders and rising stars featured in our Innovators and Ideas – Genomic Press Interview series can be found on our interview website: https://interviews.genomicpress.com/.
The Genomic Press Interview in Brain Medicine titled “Gabriella Gobbi: Embracing psychiatry from bench to bedside,” is freely available via Open Access, starting on 17 March 2026 in Brain Medicine at the following hyperlink: https://doi.org/10.61373/bm026k.0015.
About Brain Medicine: Brain Medicine (ISSN: 2997-2639, online and 2997-2647, print) is a peer-reviewed medical research journal published by Genomic Press, New York. Brain Medicine is a new home for the cross-disciplinary pathway from innovation in fundamental neuroscience to translational initiatives in brain medicine. The journal’s scope includes the underlying science, causes, outcomes, treatments, and societal impact of brain disorders, across all clinical disciplines and their interface.
One dose of the active compound in ayahuasca significantly improves depressive symptoms in early stages of a clinical trial, according to a new study.
Dimethyltryptamine (DMT), a potent natural psychedelic and a primary psychoactive component of ayahuasca, could work as an antidepressant, a study published in Nature has found.
Researchers at Imperial College London conducted a trial that demonstrated DMT’s potential to ease symptoms of depression.
Intravenous DMT has a short half-life – the time it takes for the concentration of a drug in your bloodstream to drop by half after administration – of around five minutes due to rapid metabolism.
This allows for shorter therapeutic sessions, potentially improving patient convenience and reducing costs, the research noted.
The trial is a phase 2a clinical trial, meaning a pilot study designed to provide preliminary evidence of a drug’s efficacy and to determine the most effective dose for future trials.
The number of participants is typically small, between 30 and 50, to minimise exposure to potentially ineffective treatment and to focus on a targeted patient group.
The research team in London included 34 participants who had lived with depression for an average of 10.5 years. They were randomised so that 17 received the placebo, and 17 received the active substance.
Participants received a single 21.5 milligram dose of DMT or placebo infused over 10 minutes, alongside psychotherapeutic support.
After a two-week follow-up period, those treated with DMT showed a significantly greater reduction in depressive symptoms than those who received the placebo. The effects persisted up to three months after the start of the trial.
The researchers found that DMT was well-tolerated, with no serious adverse events. Most side effects were mild or moderate, the most common being pain where the patients received the injection.
Independent experts cautioned that, while the findings are promising, further research is needed to assess the treatment’s efficacy.
“In terms of safety concerns, there may be a risk of negative experiences during the psychedelic experience that could be frightening or traumatising,” said James Stone, professor of psychiatry, Brighton and Sussex Medical School.
He added that certain groups of people may be more susceptible to these types of effects, and further studies are required to identify how often they occur.
Need for new depression drugs?
Approximately 332 million people in the world have depression, according to the World Health Organization. In Europe, more than 25 million people are estimated to live with depressive disorders.
The most common treatments include antidepressant medications and psychotherapy. However, the study authors noted that many patients experience insufficient improvement or unacceptable side effects from selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressants.
Previous research has shown that antidepressants achieve response rates of between 40 and 60 percent. Around 20 to 30 percent of patients with major depressive disorder (MDD) develop treatment-resistant depression, meaning they don’t respond to at least two different antidepressant medications.
The study authors argued that there is an urgent need for innovative and more effective treatments and suggested that psychedelics have emerged as a promising candidate.
No psychedelic treatments like DMT and lysergic acid diethylamide (LSD) currently hold full marketing authorisation from the European Medicines Agency for clinical use in Europe.
In most countries, psychedelic treatments are limited to research trials, compassionate use programmes, which allow patients with serious or life-threatening conditions to access investigational drugs outside clinical trials when no approved treatments exist, and they can't join a trial.
The Czech Republic became the first European Union country to legalise medical psilocybin – commonly known as “magic mushrooms” – for psychotherapy from 1 January 2026.
Under the new framework, the treatment is offered to people resistant to traditional depression treatments, suffering from cancer-related, severe non-psychotic, or life-threatening mental deterioration.
It can only be administered by certified psychiatrists and clinical psychotherapists with specialised psychedelic training, and in approved facilities.
