Spotlight on Health: Why Mental Health Needs New Treatment Options – PSYCH: The Psychedelics As Medicine Report 3rd Edition

Key takeaways

• According to Our World in Data, the share of the population living with mental health and substance use disorders stands at nearly 1 billion people, or 15% of the global population—a proportion that has been stable or rising since 1990.
• There have been no significant changes in mental health treatments in the last 30 years. Up to one third of people living with depression do not respond adequately to an appropriate course of antidepressant medication.
• The societal burden of depression amounts to more than US$490 billion per year in the United States alone, exceeding the societal costs of cancer or diabetes.

Psychedelics re-enter the medical conversation

For decades, psychedelics were discussed mainly in private circles—often associated with alternative healing traditions and non-Western practices. Their medical use largely disappeared from mainstream healthcare after they became closely linked to the counterculture of the 1960s. That shift contributed to a kind of collective amnesia, with many people today unaware of psychedelics’ history as legitimate subjects of scientific inquiry and clinical practice.

Prior to prohibition, psychedelics were the subject of more than 1,000 studies and were used by psychiatrists and relationship counsellors, often with reported success. More than 50 years later, psychedelics are increasingly returning to the medical conversation—while never fully leaving the public arena.

In the United States alone, 32 million people (nearly 10% of the population) have used a psychedelic at least once. Among those aged 30 to 34, 20% have tried a psychedelic. Beyond prevalence, large-scale surveys have also reported that classic psychedelic use is associated with reduced psychological distress.

From “career suicide” to mainstream science

In 2009, Dr Robin Carhart-Harris proposed studying psychedelics using functional magnetic resonance imaging (fMRI). At the time, colleagues advised against it: in the preceding 40 years, no researcher had administered psychedelics in the UK. Despite this, he continued under the guidance of Professor David Nutt, building on work from the Beckley Foundation. Their team at Imperial College London became the first to study psychedelics in the UK.

Twelve years later, there are now more than a hundred psychedelic studies being conducted each month. Established researchers such as Matthew Johnson and Roland Griffiths at Johns Hopkins Medicine have been joined by a growing cohort of investigators worldwide. Psychedelic research centres are expanding rapidly, and what was once viewed as professionally risky has become mainstream enough to reach the front pages of major newspapers, including the New York Times.

A different approach to persistent mental health problems

Psychedelics are a category of substances (mainly plant-based) with powerful psychoactive properties that alter consciousness. Most classic psychedelics—particularly LSD and psilocybin—produce their effects through interaction with the serotonergic system, altering how neurotransmitters such as serotonin and dopamine are released or absorbed and changing activation patterns in the brain.

These neurological changes can translate into psychological shifts, enabling people to approach old problems with renewed capacity. A commonly used analogy compares entrenched mental patterns to deep ski tracks: once the grooves are formed, routes become predictable. A fresh snowfall makes new paths possible again. In this framing, psychedelics may help “reset” rigid pathways, opening alternative responses and behaviours—especially when combined with psychotherapy.

This is a central distinction in treatment approach:

• Traditional medications (including many antidepressants) often aim to reduce symptoms and help people cope passively.
• Psychedelics are described here as enabling active coping—supporting a different mode of engagement with problems when paired with psychotherapy.

Mechanisms: still being mapped

Even after more than 300 clinical trials, the mechanisms of psychedelics remain an active area of investigation.

• Classical psychedelics are described as binding to a receptor that normally detects serotonin, antagonising 5-HT2a receptors.
• Ketamine is described as activating AMPA receptors and strengthening synaptic connections.
• MDMA is described as increasing activity of at least three neurotransmitters: serotonin, dopamine, and norepinephrine.
• Recent research by Awakn Life Sciences is cited as pointing toward previously unknown receptor activation by MDMA.

What is emphasised alongside these mechanistic questions is the significance of observed mental health outcomes. The most prominent study referenced is by the Multidisciplinary Association for Psychedelic Studies (MAPS). In their Phase III trial—the last stage before FDA approval—the latest data reported that 67% of participants in the MDMA group no longer met diagnostic criteria for PTSD, after suffering for an average of 15 years.

Taken together, results prior to prohibition and today’s research resurgence are presented as evidence of untapped potential—not only as alternatives to long-term conventional therapies, but as a more curative model when integrated with psychotherapy. The next step identified is regulatory validation (including FDA review) and scalable implementation of psychedelic-assisted therapy.

Key conditions under investigation

Psychedelics are being investigated for a wide range of conditions, including:

• Depression (MDD and TRD)
• Suicidal ideation
• PTSD
• Eating disorders
• Anxiety
• Substance use disorders (including alcohol, opioids, and nicotine)

The urgency is framed using global burden estimates. Our World in Data is cited as reporting that 1 billion people live with mental health and substance use disorders—15% of the world’s population—a figure described as likely to have risen during the COVID-19 pandemic. It is also noted that 7% of DALYs (disability-adjusted life years) lost to early death or disability are attributed to mental health and substance use disorders.

Treatment resistance is highlighted as a major barrier in depression care. Up to 30% of people with depression are described as treatment-resistant, meaning they have not responded positively to at least two courses of antidepressant treatment. This is stated as roughly 77 million people worldwide, likely a conservative estimate given under-treatment and non-disclosure.

Substance use disorders are described as reaching epidemic proportions in North America, including opioid dependence associated with chronic pain. The US is described as an outlier, with 3.5% of the population addicted compared to a global average of 1%, and almost 1 in 10 people aged 20–30 addicted to various substances. In 2019, 50,000 people in the United States are reported to have died from opioid overdose, whether from prescribed medications or street alternatives. Alcohol and nicotine misuse are also described as compounding these burdens.

Why the current treatment model is under strain

The text argues that conventional pharmaceuticals have had mixed success for many mental health conditions, prompting growing interest in alternatives. The widespread long-term use of antidepressants is described as a “public health experiment on a large scale” (attributed to Dr Daniel Engle), reflecting uncertainty over long-term population impacts. Negative consequences and backlash related to long-term use and/or addiction are noted, with opioids cited as a key example.

Mental health disorders are also linked to indirect mortality. Our World in Data is cited as finding that up to 90% of suicides in high-income countries can be attributed to underlying mental health or substance use disorders. Additionally, people with mental health disorders are described as facing double the risk of dying from cardiovascular disease, and the highest early-age mortality risk is described as occurring among those with eating disorders such as anorexia.

Meanwhile, the healthcare system is described as failing to keep pace. US medical spending is reported to have increased six-fold over the past 50 years, while depression and other mental health disorder rates have not decreased and may have slightly risen. The conclusion presented is that new treatment approaches are needed.

Mental health conditions by the numbers

The following figures are presented as headline estimates (millions):

• 970 — people with mental health or substance abuse disorders
• 282 — people with anxiety disorders
• 258 — people with major depressive disorder (MDD)
• 77 — people with treatment-resistant depression (TRD)
• 269 — people with PTSD
• 105 — people with alcohol use disorder (AUD)
• 70 — people with other substance use disorder (SUD)

History, culture, and the challenge of scaling responsibly

The use of psychedelics for mental health treatment is presented as relatively new within Western industrialised healthcare systems. After limited medical use in the 1960s and 70s, psychedelics largely disappeared from modern care. However, their role in healing is described as spanning millennia, embedded in diverse Indigenous traditions.

Examples provided include:

• Psilocybin mushrooms: described as used by Indigenous Australians over 10,000 years ago and by Indigenous peoples of Central America, including the Aztec term teonanácatl (“flesh of the gods”), with ceremonies continuing in Mexico.
• Ibogaine: described as used in Gabon by Bantu and Pygmy communities in Bwiti ceremonies and as a hunting aid.
• Peyote/mescaline: described as deriving from an Aztec word meaning “Divine Messenger”, with legal protections in the US under the Native American Religious Freedom Act (1994) and a 2006 US Supreme Court petition enabling ayahuasca use for a congregation’s sacraments.
• DMT: described as present in cohoba and labelled “the spirit molecule”, referencing Dr Rick Strassman’s work in the early to mid-1990s.

Johns Hopkins University’s Centre for Psychedelic and Consciousness Research is cited as examining spirituality in psychedelic studies, with multiple studies finding that subjective mystical experiences during monitored psilocybin sessions predicted sustained positive outcomes. A continuing debate is described around whether mystical experiences are primary drivers of benefit, or whether therapeutic and anti-addictive effects can be separated from hallucinogenic experiences.

The text also notes research investigating whether hallucinogenic and therapeutic effects can be separated, potentially increasing acceptance and reducing costs if prolonged clinical supervision becomes less necessary. It is specified that non-hallucinogenic analogues have, so far, been tested in mice, not humans.

The concluding challenge is framed as developing modern psychedelic-assisted therapies and medicines at scale while respecting the cultural, spiritual, and historical significance of these substances for Indigenous communities.

Why psychedelics are different from conventional treatments

The section closes by recognising uncertainty: it remains unclear how effective psychedelics will be across conditions and over the long term, and effects may depend on context and environmental change. Some studies have suggested long-lasting outcomes—for example, participants in early studies being free from anxiety for up to five years—though more research is needed to confirm durability and whether treatments must be repeated.

A key distinction is the stated goal:

• Many treatments aim to help people live with a condition.
• Psychedelics are presented here as aiming to cure, supporting “facing the music” when paired with psychotherapy.

It is also noted that not all psychedelics show the same pattern of long-lasting effects (ketamine is singled out), and that cost-effectiveness must be carefully evaluated. Upfront costs are often higher than conventional options, and widespread adoption depends on achieving meaningful outcomes for a large proportion of patients over a sustained period.