Psychedelic-assisted psychotherapy: The Australian and general practice perspective

Human societies since antiquity have used naturally derived substances to induce out-of-ordinary experiences, for example for religious or initiation ceremonies, practices that continue today in some cultures.¹ In Western medicine, an initial burst of research on psychedelic substances starting in the 1950s was shut down by the ‘war on drugs’, and it has only been in recent years that clinical research has resumed and flourished.^2,3

Australian context

The Australian Government, in setting up a $15 million research fund for psychedelics, referred to ‘a strong and emerging body of international evidence that shows that substances such as ketamine, psilocybin, and 3,4-methylenedioxymethamphetamine (MDMA), when used in a controlled environment and supported by psychological/psychiatric care, offer a promising new approach to effectively treating pernicious mental illnesses that are resistant to first-line treatments’.⁴

Although some Australian psychedelic researchers thought the decision premature,⁵ Australia’s Therapeutic Goods Administration (TGA) decided to down-schedule two psychedelic medicines – psilocybin and MDMA – from July 2023. Although they are not TGA-approved medications, they are now Schedule 8 (S8) medicines and can be prescribed outside of research trials for specific conditions (treatment-resistant depression [TRD] and post-traumatic stress disorder [PTSD]) and only by TGA-authorised psychiatrists through the Authorised Prescriber pathway.⁶ Table 1 gives some detail on the current state of evidence regarding psychedelic treatment for those specific conditions.

These medications must be used together with psychotherapy from psychotherapists trained and qualified specifically in psychedelic-assisted psychotherapy (PAT) and in an appropriately supervised environment.⁷ The TGA also regulates the quality of the supplied psychedelic medication.

Rescheduling was based on human clinical trial evidence, some of which is included in Table 1. General practitioners (GPs) can now refer suitable patients to a TGA-authorised psychiatrist for private treatment for these conditions.

Apart from this TGA rescheduling, ketamine (parenteral and sublingual) is offered as part of PAT at some private clinics in Australia under the supervision of specialist psychiatrists for conditions such as TRD and comorbid PTSD. This is an off-label use of an approved drug, using ketamine in dissociative doses to facilitate the psychotherapy, rather than the much more common use for its pharmacological actions alone. Some therapists also use tetrahydrocannabinol (THC)-dominant cannabis for PAT,⁸ a medication that is legal but not TGA approved.

What are psychedelics?

A psychedelic can be defined as a substance that induces temporary but significant altered states of consciousness, including sensory perception, thoughts and emotions.⁹ These experiences can include sensory hyperacuity, dissociation, hallucinatory perceptions and expressions from the subconscious.³ They can be intense and challenging experiences, as well as inducing profound feelings of peace and connection with others, within oneself and with a broader, more universal reality. These effects can produce major shifts in previously rigid perspectives and patterns of thought, self-image and emotion, including to the emotional and somatic intensity of traumatic memories.¹⁰ Refer to Table 2 for psychedelics in common clinical use.

Do psychedelics work?

Clinical trials continue to clarify indications, efficacy and safety. For now, it is important to understand that not everyone is suited to, safe for or will respond to PAT, and some people may feel worse during or after treatment. Randomised trials must overcome problems of unblinding and patient pre-expectation, but overall meta-analyses of trial results have shown some substantial effect sizes.

In depression, for example, one could compare the benefit found in a meta-analysis of psilocybin trials (standardised mean difference [SMD] = –0.78, P<0.001)¹¹ with the effect size consistently reported in antidepressant trials of approximately –0.3.^12,13 Similarly, one can compare in PTSD the effect size on symptom score in a meta-analysis of MDMA (SMD=–0.78)¹⁴ with that in a meta-analysis of selective serotonin reuptake inhibitors (SSRIs; SMD=−0.28).¹⁵

Evidence suggests that approximately two-thirds of patients with PTSD will experience remission on MDMA,¹⁶ whereas 57% of patients with depression will respond and 45% will experience remission on psilocybin.¹¹ On an individual level, many patients experience in short time frames (ie weeks) substantial improvements in clinical symptoms that had remained refractory after years of conventional treatment, going from severe PTSD to no longer meeting criteria for diagnosis.¹⁷

How do psychedelics work?

Biological mechanisms remain under investigation, but the ‘classical’ psychedelics exert their neurobiological effects via agonism at the serotonin 2_A receptor.⁹ Evidence suggests that psychedelics temporarily alter communication between large-scale brain networks (eg default mode and salience networks) and can induce a period of neuroplasticity such as can allow new learning to take place.^18–20

How is it done?

PAT treatment usually involves some time in preparation, up to three dosing sessions and a series of psychotherapeutic integration sessions, which help the patient to make sense of their experience and to preserve, protect and extend what is valuable within it. Most but not all treatment plans require two psychotherapists working together.

Importantly, the benefits of this combined psychedelic–psychotherapy approach, with the right patient mindset and a safe external setting, go far beyond what people normally experience using these drugs recreationally (eg taking ecstasy at a party).²¹

In Australia, PAT is being conducted within university and industry clinical trials and in private hospitals and clinics. Although costs vary, unfortunately the expense of the medicine and particularly psychiatrist/psychotherapist time means that a course of privately undertaken PAT is expensive, ranging widely but up to $35,000, although some limited rebates may be available. For example, one of Australia’s largest private health insurers has confirmed that it will begin rebating MDMA treatment for PTSD.²²

A substantial commitment is required of the patient, including commitment both to change and of time.

What to expect from the treating team

You can expect the PAT treating team to be helpful in answering your questions about the treatment and whether your patient is suitable for referral. They will be proactively interested in your perspective on the patient’s psychiatric and psychosocial background (including family and social supports) and physical comorbidities. The team should keep you informed of progress during treatment, perform a good handover at the end and have some helpful ideas regarding ongoing support if required (eg names of some PAT-aware psychotherapists). Refer to Box 1 and 2.

Role of the GP

Referral

GPs may consider referring privately to an authorised psychiatrist a patient who has failed conventional treatment for:

• depression – psilocybin
• PTSD (including complex PTSD) – MDMA.

Clinical trials will provide free treatment, and it is worth checking trial registries to see if any are recruiting.^23,24 Other conditions that have been or are planned to be treated in Australian PAT trials include: end of life, addiction, eating disorder, obsessive–compulsive disorder, generalised anxiety disorder and autism.³

Referral for ketamine-assisted psychotherapy should be through a psychiatrist familiar with it.

Although PAT within proper clinical care with well-selected patients has a good safety record,^25,26 contraindications would typically include a personal or first-degree family history of psychotic illness,²⁵ possibly bipolar disorder and active drug addiction (although the latter two conditions have been targets of PAT trials).^25,27 PAT does not appear to itself induce addiction to the medications used.²⁸

Patient education

The GP may like to provide evidence-based education about PAT to counter both unfounded fear and unrealistic expectations.

Deprescribing

As some conventional medications have potential adverse interactions with psychedelics (eg SSRIs/ serotonin–noradrenaline reuptake inhibitors for serotonin syndrome) or can interfere with the therapeutic effect (eg sedatives, alcohol),²⁹ patients may need to come off these before dosing. Deprescribing can be a challenge, possibly one on which the authorised psychiatrist might ask you to work with them as the doctor who has a long-term relationship with the patient. Less deprescribing is required for ketamine.

Support during treatment

Undergoing PAT can be transformative but also a vulnerable or confronting experience and, frankly, hard work at times. It is important that you, as the steward of your patient’s holistic care, be open-minded about their undertaking a novel treatment so that they feel they can talk openly to you about it, even if they have some difficulty expressing the inexpressible. This helps your patient’s confidence that they have a united team supporting them.³⁰

The patient may experience some of the common post-dose effects; working with their PAT team, you can reassure your patient about these symptoms and help the patient cope with them. The most common symptoms can be muscle tightness or headache, as well as feelings of physical or emotional flatness or lability in the days after dosing. Challenges of adjusting to a new mindset and newly felt emotions can arise in subsequent weeks.

A rare condition, hallucinogen persisting perception disorder, involves sensory distortions continuing well after the psychedelic drug has left the system. This has mostly been seen with lysergic acid diethylamide (LSD) and in recreational rather than clinical settings.³¹

Handing back

Open-mindedness is also needed after the patient completes PAT. They may well want to talk to you about what has happened or seek a referral to a psychotherapist who understands PAT, especially if they have come from a clinical trial where the psychotherapy has a definite end date. Although the field is too young to have standardised credentialling, the team that has been providing PAT may well know a locally based, qualified colleague.

Getting involved

For any GP interested in participating in PAT, there are a number of organisations and common interest groups offering peer support, membership and training. But, as stated above, the field does not yet have standardised training or credentialling. The Royal Australian and New Zealand College of Psychiatrists has published a training guideline with a syllabus for psychiatrists.³² Getting involved in a university clinical trial is one option, and Table 3 contains some others.

Conclusion

The TGA rescheduling of two psychedelic medications for use with psychotherapy in Australia has brought what had been cutting-edge treatment with much potential but still under investigation into the reach of GPs who may wish to refer their patients to a TGA-authorised psychiatrist.

The current place for PAT is for patients who have failed conventional treatments, such as for PTSD or depression. The clinical evidence so far shows good results for the majority of such patients, with effect sizes well above those of conventional treatments.

However, PAT does not work for everyone and can be challenging even for those for whom it does. Not every patient who may be technically eligible will be suited. Appropriate psychological or psychiatric support after a course of PAT is essential.

The GP, working with the authorised psychiatrist and their team, can make a significant contribution to the ongoing evaluation of this treatment in Australian patients.

Key points

• Psychedelic medicines as part of a course of psychotherapy represent an exciting new development in psychiatric medicine that offers hope for patients with treatment-resistant conditions such as depression and PTSD.
• This is still cutting-edge psychiatry very much under clinical trial study, but results so far show effect sizes well above that of many conventional psychiatric treatments.
• Not every patient is suited to, safe for, can afford or will respond to this treatment; careful patient selection is required.
• When done with appropriate patients by experienced clinicians, PAT is a safe treatment. However, it can be quite hard work for the patient psychologically as it can bring up uncomfortable emotions and memories, challenge existing mindsets and involve significantly out-of-ordinary experiences.
• GPs have a role to play in selecting appropriate patients for referral, informing patients but also tempering unrealistic expectations and supporting them during and after treatment as part of their mental health team.