Key Insights

• According to Our World in Data, the share of the population with mental health and substance use disorders stands at nearly 1 billion people, or 15% of the world 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 a third of those suffering from depression do not respond adequately to a course of appropriate antidepressant medication.
• The societal burden of depression amounts to more than US$490 billion per year for the US alone, eclipsing the societal costs of cancer or diabetes.
• Psychedelics as medicines offer a way to solve mental health and substance use disorders, leading to possible savings of over US$680 billion if scaled up.

Psychedelics Coming Out of the Closet

Psychedelics have long been something that one only spoke about, in intimate circles, with reference to alternative healing and traditional medicine. The banishing of psychedelics as medicines, after they became synonymous with the counterculture of the 1960s, has led to collective amnesia, with many people today unaware of the rich history of psychedelics prior to their ostracism. Not only were psychedelics the focus of more than 1,000 studies, but they were also used by psychiatrists and relationship councilors with great success.

Now, over 50 years after psychedelics have left the public consciousness, they are rejoining the conversation. That is the medical conversation; psychedelics have never left the public arena. In the US alone, 32 million people, which is nearly 10% of the population, have used a psychedelic in their lifetime. Among those aged 30 to 34, 20% have tried a psychedelic. It is not only that psychedelic use is commonplace, but large scale surveys have also shown that classic psychedelic use is associated with reduced psychological distress.

In 2009, the young, eager researcher, now Dr. Robin Carhart-Harris, told his colleagues he wanted to focus his research on psychedelics and study them using functional magnetic resonance imaging (fMRI). Many advised him against this path. In the 40 years prior, no other researcher had administered psychedelics in the UK. Yet, he persisted and under the guidance of Professor David Nutt and building on the work by the Beckley Foundation, their team at Imperial College London became the first to study psychedelics in the UK.

Now just 12 years later, there are more than a hundred psychedelic studies being conducted each month. Established drug researchers such as Matthew Johnson and Roland Griffiths at Johns Hopkins Medicine are joined by a slew of younger researchers from all over the world. Psychedelic research centres are growing like mycelium across the world and from what was originally perceived to be ‘career suicide’, psychedelic researchers are now making it to the front page of the New York Times.

Novel Way of Treating Persistent Problems

Psychedelics belong to a category of substances (mainly plant-based) that possess powerful psychoactive properties, meaning that they change someone’s state of consciousness. Most psychedelics, especially the classic psychedelics, LSD and psilocybin, achieve their mind-altering effects through interaction with
the serotonergic system. By changing how serotonin, dopamine, and other neurotransmitters are either released or absorbed, psychedelics change activation patterns in the brain.

These neurological changes also emerge at the psychological level where this altered state allows one to tackle old problems with renewed vigour. One way psychedelics can be viewed is that they allow someone to break free from old patterns or tracks. Imagine a ski slope where, after an intense day of skiing,
your next run down the mountain is already predetermined. The grooves are deep and small moguls force you to take one, of only a few routes, down. Wait a night and for some fresh snow to fall, and novel ways down the mountain become available again. A fresh ski slope, just like a brain influenced by psychedelics, offers a mountain of possibilities.

It is this process that happens both at the neurological and psychological level. Psychedelics by themselves do not solve any problems, they only allow one to take action and broaden the options available, especially in combination with psychotherapy. Where traditional medications such as antidepressants aim to relieve the symptoms of the suffering one experiences (passive coping), psychedelics allow one to see problems with a fresh set of eyes (active coping).

Even after more than 300 clinical trials, we are still discovering the many processes through which psychedelics work. Classical psychedelics work by binding to a receptor that normally detects serotonin (antagonising the 5-HT2a receptors). Ketamine, on the other hand, works by activating AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and strengthening synaptic connections. MDMA increases the activity of at least three neurotransmitters; serotonin, dopamine and norepinephrine. We are still discovering the different ways in which psychedelics work in the brain. Recent research by Awakn Life Sciences points towards previously unknown receptor activation by MDMA.

What we do know is that the mental health outcomes are significant and promising. The most prominent study to date has been done by the Multidisciplinary Association for Psychedelic Studies (MAPS). The latest data from their phase III clinical trial, the last step before Food and Drug Administration (FDA) approval,
is showing that 67% of the participants in the MDMA group no longer met the diagnostic criteria for post-traumatic stress disorder (PTSD); participants who had previously been suffering for 15 years on average.

The promising results before prohibition, combined with the resurgence of research, show the untapped potential that psychedelics offer. This is not only as a replacement of often ineffective and life-long conventional therapies, but as a curative model when combined with psychotherapy. The next step that is required is validation by the FDA and the implementation of psychedelic-assisted therapy at scale. Psychedelic medicines, both naturally occurring and those synthesised, have the potential to redefine how mental health conditions will be treated.

Key Conditions

Psychedelics as medicines are being investigated for the treatment of a wide range of mental health disorders such as depression (MDD, TRD), suicidal ideation, PTSD, eating disorders, anxiety and substance use disorders (SUD), such as addiction to alcohol, opioids and nicotine.

This is needed now, more than ever before, as, according to Our World in Data, 1 billion people are suffering from mental health and substance use disorders. This amounts to 15% of the world population, a number that has surely risen during the COVID-19 pandemic. For every year that is lost due to early death
or disability (DALYs – disability-adjusted life year), 7% is caused by mental health and sub stance use disorders. The cost to society of depression has surpassed that of cancer and doesn’t look to be going down without finding new solutions.

Up to 30% of people with depression are treatment-resistant (TRD), meaning their condition has not responded positively to at least two courses of antidepressant treatment. This equates to roughly 77 million people suffering from TRD worldwide. It is likely that this figure is a conservative estimate given that many people suffering from mental health problems, such as depression, choose not to seek help for their condition.

Substance use disorders (SUDs), including dependence on opioids, for conditions such as chronic pain, have reached epidemic proportions, particularly in North America, where even conservative estimates place the cost to the US economy at tens of billions of dollar in lost earnings every year. The US stands out
from the global average of 1% of the population with SUDs with 3.5% of the population being addicted, and almost 1 in 10 people between 20 and 30 addicted to various substances. In 2019, 50,000 people in the US alone overdosed on opioids, either from prescribed medications or their street alternatives. Other substance misuse conditions, such as alcoholism and nicotine addiction, exacerbate the problem. Conventional pharmaceuticals, prescribed for these and other mental health conditions, have had varying success to date and companies are now looking elsewhere for solutions.

The widespread and long-term use of traditional antidepressants has been dubbed as a ‘public health experiment on a large scale’ according to Dr Daniel Engle, as nobody truly knows what the impact will be on public health or on those individuals who have spent many years on antidepressants. Already we are seeing many conventional pharmaceutical products experience a backlash from the negative side effects of long-term usage and/or addiction, with opioids – the bedrock of the pharmaceutical industry – being a key example of this. There is a definite appetite for alternatives to conventional medicines among patients.

Mental health disorders also lead to a significant number of indirect deaths through suicide and self-harm. Our World in Data finds that up to 90% of suicides in high-in come countries can be attributed to underlying mental health or substance use disorders.

In addition, those suffering from mental health disorders face double the chance of dying from cardiovascular diseases. The risk of dying at an early age is highest for those suffering from eating disorders, such as anorexia.

In a world that is spinning around ever faster, the health care system isn’t able to keep up. Spending on medical care has gone up 6-fold in the United States over the past 50 years. In that time, the rate of depression and other mental health disorders hasn’t budged or has slightly risen. It is time for a new way forward.

Psychedelic History and Future

Using psychedelics to treat mental health conditions is a new development in Western and industrialised countries. After briefly being used in the 1960s and 70s, psychedelics have not had a place in modern-day health care. But, their role in society and their potential to heal, has been documented over millennia and is recognised by many diverse indigenous communities around the world.

Psilocybin mushrooms have a long history of traditional use – from indigenous Australians over 10,000 years ago, to the ancient native peoples of Central America (particularly in Mexico), who believed that psilocybe mushrooms were sacred. The Aztec people referred to mushrooms as teonanácatl or ‘flesh of the gods’. Healing ceremonies are still held in Mexico today, led by native shamans known as curandera.

In West and Central Africa, ibogaine has traditionally been used by the Bantu and Pygmy communities of Gabon, specifically in Bwiti religious ceremonies and as an aide to healing. Certain peoples of Gabon and the Congo region have also used iboga extracts, or chewed the root of the plant, in order to remain calm, but alert, whilst hunting animals.

The word ‘peyote’, the name given to the cactus from which the psychedelic substance mescaline is derived, comes from an ancient Aztec word, which translates as ‘Divine Messenger’. Under the Native American Religious Freedom Act, 1994, Native American peoples living in the US have a legal right to use peyote
as part of religious ceremonies. One Native American congregation successfully petitioned the US Supreme Court in 2006, to allow its members to use ayahuasca as part of its religious sacraments.

DMT, one of the main components of ayahuasca, can also be found in cohoba, a hallucinogenic snuff used by the Indians of Trinidad and by the Llanos in northern South America during the earliest explorations of the continent by the Spanish. DMT has been dubbed ‘the spirit molecule’, a nickname taken from
the popular book of the same title, by Dr. Rick Strassman, who examined how DMT produced mystical and near-death experiences in study volunteers in the early to mid-1990s.

The Centre for Psychedelic and Consciousness Research at Johns Hopkins University has also undertaken research to examine the importance of spirituality among participants in psychedelic studies. A number of these studies have found that subjective mystical experiences (for example during monitored
sessions while using psilocybin) were an accurate predictor of sustained positive responses among participants. Currently, a debate is ongoing within the scientific community, to understand in what ways mystical experiences contribute to the positive long-term effects that psychedelics engender. Where some researchers argue that such experiences of awe are the key driver of mental health benefits, others are researching ways to separate the mental health and anti-addictive effects from the mind-altering perceptions.

The latter group is also investigating if we can separate the hallucinogenic and therapeutic effects of psychedelics. Blasphemy to some; separating these effects could lead to a wider acceptance of psychedelics as medicines and for them to be used by those who would rather not experience changes in their consciousness. If found to work in humans, as studies with non-hallucinogenic analogues have only been completed in mice, these could also save costs where a qualified medical professional does not have to sit with a patient for several hours anymore.

The challenge going forward will be to utilise the healing properties of psychedelics, something indigenous communities have been doing for hundreds, if not thousands of years, to develop modern psychedelic-assisted therapies and medicines, while also scaling up the process to meet global demand. Psychedelic s medicine should benefit a new generation of patients suffering from a broad range of mental health conditions, while also respecting the cultural, spiritual and historical importance of these substances to indigenous communities.

Why psychedelics are different?

The jury is still out on how effective psychedelics will be in the treatment of mental health and substance use disorders. Early studies on everything from smoking cessation to PTSD show the significant and often lasting impact of psychedelics. But, not in all cases does depression stay away and without changing their environment, how long can we expect treatment effects to last? What will prevent psychedelics from becoming the next ineffective treatment?

The key difference between psychedelics and other treatments is that the methods and goals are completely different . Whereas many treatments are aimed at helping someone live with a condition and making life livable again, psychedelics aim to cure. Psychedelics are activating and can help, in combination with psychotherapy, someone to ‘face the music’.

This also means that psychedelic therapies are not a pill or treatment that someone has to take every day for the rest of their life. Some early psychedelic studies have shown that participants were free from anxiety for up to five years. More studies will have to show if these effects are sustained or whether psychedelic treatments need to be repeated months or years later.

These effects have been found in early clinical trials and for the classical psychedelics that are detailed in this report, but this is not for all psychedelics, such as ketamine. The cost-effectiveness to society needs to be carefully examined, as the upfront costs of psychedelic treatments are often much higher than that of other therapies. Only if PAT is able to help a large proportion of those treated, and for a long period of time, can we expect them to find widespread adoption