Psychedelic medicine: A mental health game changer?

Mental health disorders are widespread, so it’s critical we have a breadth of effective therapies available. Now, plant-based psychedelic compounds are showing emerging promise.

The following opinion piece co-authored by Professor Jerome Sarris, NICM Health Research Institute, Professor Nicole Leite Galv√£o-Coelho, NICM Health Research Institute and Dr Daniel Perkins, University of Melbourne, was first published with full links on Pursuit.(opens in a new window)


12 January 2021

About 20 per cent (opens in a new window) of Australians struggle with a mental illness every year, ranging from depression and anxiety to substance or alcohol abuse.

The potential hardship and isolation posed by COVID-19 risks leaving more people vulnerable.

While we are fortunate to have a range of pharmaceutical and psychological treatments for mental illness, these may not be effective in some people, or at least they may still leave people with residual symptoms. Additionally, there are usually some side effects which commonly occur from drug therapies.

Given the scale of mental illness in society, innovative new treatment approaches are urgently needed.

One of these new approaches is the medicinal use of previously prohibited psychotropic plant-based medicines such as cannabis, or psychedelic compounds such as ‘magic mushrooms’.

For example, there has been a resurgence of research interest in cannabis that by the end of 2020 around 80,000 Australian approvals (opens in a new window) will have been granted to prescribe medicinal cannabis since November 2016.

The next evolutionary step is for additional psychoactive compounds to be rigorously assessed in safe clinical and scientific models.

To this end, there have been a rising number of studies on a range of other plant-derived and related psychotropic compounds for psychiatric disorders.

Examples include psilocybin (the compound found in magic mushrooms), ayahuasca (opens in a new window) (a two-plant combination originating in the Amazonian basin, which has been used in shamanic applications for centuries), the North, Central and South American peyote and the San Pedro cacti which both contain the psychoactive compound mescaline, and even LSD (lysergic acid diethylamide), the well-known synthetic hallucinogen popularised in the 1960s.

These psychedelics work, in part, in a similar way to traditional antidepressants ­– they affect the chemical pathways in the brain involving serotonin (the hormone that influences mood and can make us feel good).

However, they also have a range of other beneficial biological activities, like anti-inflammatory effects.(opens in a new window)

Potential areas of therapeutic application of psychedelics include treating depression, substance or alcohol addiction, healing trauma and assisting in addressing end-of-life anxiety.

These mental health conditions often co-occur, which increases the clinical complexity and can worsen the overall prognosis.

So, what’s the current evidence for the effectiveness of these medicinal psychedelics for mental health disorders?

We recently conducted, at Western Sydney University’s NICM Health Research Institute, the first ‘meta-analysis’ (pooling data from clinical trials for analysis) involving both healthy adults and those with clinical mood disorders to evaluate the clinical effects of psychedelic agents versus placebo on mood state and symptoms of depression.(opens in a new window)

Our literature research found 12 eligible studies undertaken over the last decade involving 257 participants (124 healthy participants, and 133 patients with mood disorders).

The data was from randomised controlled trials involving psilocybin (eight trials), LSD (three trials), and Ayahuasca (one trial).

Our analysis (opens in a new window) shows that medicinal psychedelics have a statistically significantly superior effect to placebo on improving negative mood outcomes and symptoms of depression over the short-term (three hours to one day after treatment) and longer-term (16 to 60 days after treatments) for patients with a mood disorder.

The best results for depressive symptoms were achieved within two-to-seven days. Additionally, short-term mood enhancement was also observed for people who were mentally healthy and didn’t have depression.

Importantly, the data suggests that medicinal psychedelics have a good safety profile, though they are strongly not recommended for people with a personal or family history of psychosis – schizophrenia, for example.

Transient reactions may also occur in some people, like anxiety or panic, or a mild increase in cardiovascular function. It’s therefore vitally important to have medical support at hand if required.

We also have compelling data (opens in a new window) showing that the psychedelic formulation Ayahuasca may also be of benefit in treating depression as well as substance/alcohol addiction and abuse.

The Global Ayahuasca Project (opens in a new window) (GAP) is a University of Melbourne-led observational survey undertaken across 2017-2020 involving 10,838 people who reported use of Ayahuasca.

The results (which have been submitted and are under review at two academic journals) revealed that consumption of the plant brew was associated with reduced alcohol and drug use, as well as enhanced psychological wellbeing and better mental health.

Around 65 per cent of all respondents reported drinking alcohol less frequently since first consuming ayahuasca. Among the 708 individuals identifying as having an alcohol problem at the time of drinking ayahuasca, 89 per cent reported their condition ‘much improved’ or ‘completely resolved’ as a result of their ayahuasca consumption.

Similarly, of 1571 participants who identified as having depression at the time of ayahuasca consumption, 78 per cent reported that their depression was now either ‘very much’ improved or ‘completely resolved’.

It’s important to note that it is vital the study and potential use of psychedelics is carried out within a psychotherapy-supported and medically-supervised framework.

The psychological treatment model for the medical use of serotonin-inducing psychedelics is a critical aspect which substantially differentiates it from other drug therapies. This focus is known as ‘set and setting’.(opens in a new window)

The optimisation of these factors through appropriate preparation with a trained clinician, along with support before, during and after an acute experience, can facilitate emotional and trauma processing.

This is important if the patient is to take on the new perspectives, sense of meaning and enhanced self-understanding that are also important for the clinical change needed in mental health disorders and addiction.

The strength of the acute clinical effect, fast onset, and enduring therapeutic effects of these psychotherapeutic agents should encourage further larger clinical trials to assess them across a range of mental health applications.

We know that more research is already being conducted around the globe on a range of agents for several psychiatric conditions.

If their safety and efficacy can be proven by further robust research, there is real potential for medicinal psychedelics to be used as a new therapeutic option within dedicated medically-supervised facilities in Australia, involving trained clinical psychologists.

This would provide a game-changing option, especially for currently intractable mental health disorders.

If you have any mental health concerns, please contact your GP, or if you or anyone you know is experiencing a mental health crisis, please contact Lifeline(opens in a new window) on 13 11 14.