Psychedelic Assisted Therapy

If there were ever a therapeutic approach that would be met with a little scepticism, it would most probably be psychedelic-assisted psychotherapy.

‘Standard’, ‘regular’ or more mainstream therapy can be challenging, intense and unpredictable, so could adding hallucinogenic drugs into the mix really help the process? The short answer is yes – maybe.

Unfortunately, in many places around the world, including here in NZ, the use of psychedelics has been stalled due to laws surrounding substances like LSD and Ketamine. Despite this restriction, there has been some interesting research exploring psychedelic-assisted psychotherapy, linking this to a resurgence of clinical interest in recent years, and we have promising findings around psychedelic-assisted therapy.

In this article, we explore a little further into psychedelic-assisted therapy, focusing on some ground-breaking research that explores the effectiveness and safety of psychedelic-assisted therapy to treat a range of mental health conditions, like depression, trauma, PTSD, addiction, and anxiety.

What Is Psychedelic Assisted Therapy?

Psychedelic-assisted therapy usually involves ‘talk therapy’ alongside the ingestion of a classical psychedelic such as LSD, psilocybin, or ayahuasca. Clinicians and researchers often describe three distinct therapy phases:

preparation,
the acute psychedelic experience,
and integration.

The non-psychedelic components of this approach are essential for both safety and effectiveness.

What are Psychedelics?

Psychedelic drugs can alter perception and consciousness, often provoking visual or auditory hallucinations and dream-like encounters.

As defined by Oxford, psychedelics describe substances that lead to an “apparent expansion of consciousness,” which essentially celebrates their positive and potentially helpful mind-broadening potential.

Psilocybin, a naturally transpiring psychedelic compound found in ‘magic mushrooms,’ has a molecular structure that allows it to penetrate our central nervous system. Scientific and medical experts are only just beginning to comprehend its effects on the brain and its potential as therapeutics for mental illnesses.

Some drugs used in psychedelic-assisted therapy include:

Psilocybin — 4-phosphoryloxy-N,N-dimethyltryptamine
LSD — lysergic acid diethylamide
MDMA — 3,4-methylenedioxymethamphetamine
Ibogaine — 12-methoxyibogamine
Ketamine — 2-(2-chlorophenyl)-2-(methylamino)cyclohexane-1-one

Mental Health Conditions and Psychedelic Assisted Therapy?

While the research on psychedelic medicine for mental illness is still in its infancy, considered new and emerging, some studies have shown fascinating and compelling results.

Studies trialling different psychedelics have been concluded by looking at various mental health conditions (like anxiety, depression, PTSD, trauma and addiction). Early results are promising, linking certain psychedelics with specific mental health conditions. In summary, psychedelics have been trailed and shown positive results across the following areas:

Depression
PTSD
Anxiety related to terminal illness.
Substance use disorder – Alcohol, drugs, nicotine.
Refractory (Treatment-resistant) anxiety
Acute suicidality

Additionally, psychedelics can offer an array of benefits for psychotherapy, such as:

Facilitating meaningful, positive, or “mystical” psychological experiences
Strengthening therapeutic relationship
Improving introspection and awareness of feelings, thoughts and memories
Helping to process and regulate difficult emotions.
Enhancing cognitive creativity and flexibility.

Psilocybin

Psilocybin was used in a study by Johnson and other researchers where 51 patients with life-threatening cancer diagnoses. These patients also suffered from depression or anxiety. It was discovered that high-dose psilocybin improved quality of life and symptoms when given with psychological support. About 80 per cent of participants, after six months, continued to show clinically significant decreases in anxiety and depressed mood.

A further study by Johnson and his team reported that two doses of psilocybin significantly reduced depressive symptoms. This smaller research group consisted of 15 adults with major depressive disorder (MDD), their results were compared to a controlled group of 12 adults who received no treatment. Impressively, more than half the study participants were in remission four weeks after treatment.

LSD

LSD-assisted psychotherapy consists of a combined intervention of therapy and medication. According to a study with 12 participants, it is thought to reduce feelings of anxiety among people diagnosed with life-threatening illnesses who are anxious about their illnesses. Encouragingly, follow-up research with the same participants one year later found that those reductions in anxiety had lasted.

A review of 6 clinical trials with 536 participants linked a single dose of LSD to a decrease in alcohol misuse. LSD was administered as part of treatment programs for alcohol use disorder.

Ketamine and Esketamine

Intranasal esketamine (via the nasal passage), administered together with standard antidepressant treatment, has been shown, in a small 2018 study, to significantly reduced depressive symptoms and suicidal thoughts among high suicide risk patients with depression.

In another 2018 study, ketamine administered alongside ongoing antidepressant treatment was discovered to significantly reduce suicidal thoughts and behaviours within 24 hours.

And in a more elongated study conducted between 2016 and 2020, researchers discovered that among 537 people who, in a clinical setting, received intravenous ketamine therapy, more than half of patients experienced an improvement in their symptoms, with nearly 30 per cent achieving remission. Additionally, 73 per cent of people with suicidal thoughts and behaviours saw a decrease in these symptoms. Researchers noted that 8 per cent of people experienced worsened depression after starting.

MDMA

Some of the most effective results for MDMA as a treatment for mental illness have arrived from clinical trials involving people with PTSD. A study with 90 participants found that 67 per cent of people treated with MDMA-assisted therapy no longer satisfied the diagnostic benchmarks for PTSD after 18 weeks of treatment.

The authors of the study concluded that “MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.”

Psychotherapy Support

It’s important to note that currently available research consists of very small, short-term studies. Many of these studies were performed in specific groups of patients, meaning that the findings from these studies may not apply to everyone. Although this initial research is promising, it’s essential to note that these studies involved extremely careful administration of these drugs under the supervision of doctors in a clinical setting.

Additionally, many studies also included supportive care in the form of psychotherapy. “For clinical indications, psychotherapy appears to be necessary to support and facilitate change,” says Danovitch – MD, a professor and chair of the department of psychiatry and behavioural neurosciences at Cedars-Sinai Medical Center in Los Angeles.

Danovitch adds that therapy protocols typically involve the following phases:

Assessment phase During this phase, the patient and a mental health professional set goals for therapy.
Preparation phase This phase aims to get patients emotionally and physically ready for treatment.
Experience phase During this phase, the medication is taken while health professionals monitor patients carefully.
Integration phase This phase focuses on, after treatment with the psychedelic has ended, helping patients reflect and learn from the experience.

Kelley O’Donnell, MD, PhD, an assistant professor of psychiatry at the New York University (NYU) Grossman School of Medicine and a researcher at the NYU Langone Center for Psychedelic Medicine, says ‘this type of support, including preparing the patient for what will happen when taking the medication, is vital for successful treatment’.

“If someone has no idea what they’re in for and someone gives them a psychedelic, that can be a really traumatic experience,” O’Donnell says. “A lot of people have the idea that it’s a one-and-done and your life is transformed forever, and that’s really not the case. That takes it out of the context of a therapeutic relationship, which is so important.”

New Zealand – Ketamine Study

More recent studies into psychedelics conducted by Auckland-based Dr Suresh Muthakumaraswamy say.

‘These days, a leading theory is that psychedelics diminish activity in the “default mode network,” an area of the brain involved in maintaining a sense of self and engaging in self-reflection.’

A world-first clinical trial conducted in Auckland showed the effect of ketamine on patients with serious depression. In the image above, the orange areas show the increased ‘plasticity’ or better connections between synapses in the brain recordings of patients in the trial. It’s this increase in ‘plasticity’ that is important in reducing the symptoms of depression so fast.

The default mode network is the area where addicts or people suffering from depression would reflect on self-defeating stories of their lives. Researchers speculate that temporarily limiting the default mode network allows for the spiritual experience known as “ego dissolution” or “ego death“. These terms refer to a temporarily diminished sense of self, and the feeling is usually captured by statements like ‘I lost all sense of myself’ or ‘I felt at one with the universe’.

It’s thought that this could potentially help addicts and people suffering from depression to break free from repetitive patterns of thinking.

Additionally, Muthakumaraswamy and Rachael Sumner (who conducted the ketamine study) noted one key avenue of exploration is the theory that psychedelics enhance neural plasticity. Neural plasticity is the ability of brain cells to form new connections. That ability may be diminished in people who suffer from depression or who are trapped in repetitive behaviours such as addiction or obsessive-compulsive disorder.

Between 2016 and 2018, in the ketamine study, 30 people with treatment-resistant depression were infused intravenously with ketamine and then scanned in an MRI machine.

Three or four hours later, after the psychedelic effects had faded and having rested and eaten, the volunteers were wired up to an EEG Machine (electroencephalography) to monitor their brains as they focused on a red dot on a screen as black and white images flashed past.

This task allowed scientists to witness ‘long-term potentiation” or strengthening of synapses in response to a stimulus‘. This is a positive sign indicating increased neural plasticity.

The study showed impressive results in most of the volunteers. With their depression symptoms falling by 50 per cent or more within a day, these improvements faded after a week or so. Although there was a return of symptoms, in some cases, volunteers found hope by simply knowing they were capable of feeling happier.

Johns Hopkins Research – Psilocybin Research

The Johns Hopkins Center for Psychedelic and Consciousness Research is pioneering the way in exploring innovative treatments using psilocybin. Researchers build on prior work and extend research on psychedelics for wellness and illness, with a focus on two key areas:

Develop new treatments for a larger variety of psychiatric and behavioural disorders with the aspiration of treatments tailored to the distinct needs of individual patients
To expand research on volunteers who are healthy with the ultimate aspiration of opening new ways to support human thriving.

A previous 2020 study completed by Johns Hopkins Medicine researchers showed that psychedelic treatment with psilocybin relieved major depressive disorder (MDD) symptoms in adults for up to a month. A recent (2022) follow-up study of those same participants reported substantial antidepressant effects of psilocybin-assisted therapy (supported with psychotherapy), lasting at least a year for some patients.

Natalie Gukasyan, M.D, assistant professor of psychiatry and behavioural sciences at the Johns Hopkins University School of Medicine, says

Natalie Gukasyan, M.D, assistant professor of psychiatry and behavioural sciences at the Johns Hopkins University School of Medicine, says, “Our findings add to evidence that, under carefully controlled conditions, this is a promising therapeutic approach that can lead to significant and durable improvements in depression,” However, she cautions that “the results we see are in a research setting and require quite a lot of preparation and structured support from trained clinicians and therapists, and people should not attempt to try it on their own.”

The last 20 years have seen a growth in research with classic psychedelics. Within research settings, treatment with psilocybin has shown promise for treating a range of mental health disorders and addictions.

In this Johns Hopkins study, researchers recruited 27 participants with a long-term history of depression. Most participants had been experiencing depressive symptoms for around two years before recruitment.

Participants were randomised into two groups in which they either received the intervention immediately or after an eight-week waiting period. Participants received two doses of psilocybin, given approximately two weeks apart. For the next 12 months, various follow-up sessions were attended where assessments of each participant were conducted.

Researchers reported that psilocybin treatment in both groups produced significant decreases in depression and that depression severity remained low at each of the follow-up assessments scheduled at one, three, six and 12 months after treatment. Depressive symptoms were measured using the GRID-Hamilton Depression Rating Scale, in which a score of 24 or more indicates severe depression, ranging down to 17–23 moderate depression, 8–16 mild depression and seven or less no depression.

For the majority of participants, scores for the overall treatment decreased from 22.8 at pretreatment to

8.7 at one week
8.9 at four weeks
9.3 at three months
7 at six months
7.7 at 12 months after treatment

“Psilocybin not only produces significant and immediate effects, but it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression. Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments.”

– Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research.

Different Thinking

As a country, we are in the middle of a mental health crisis. Never has there been more of a need for us to be thinking differently about how we treat all mental health conditions. Our NZ statistics are startling; Antidepressants are taken by more than 400,000 people. According to a 2018 report on mental health and addiction, around 20,000 people attempt to kill themselves each year, while an overall suicide rate of 13.93% per 100,000 people is doubled for Māori.

Even more staggering is the youth suicide rates, with NZ being among the worst in economically developed nations.

With traditional avenues of mental wellness care overwhelmed, with long wait lists to see experts and hourly rates for treatment automatically limiting access. We should be working harder to see treatment through an alternative lens. Thinking less about medicating feelings with sleep medication and antidepressants and exploring alternative options that help reduce symptoms and get to the root cause of the mental and physical impacts of anxiety, depression, trauma, PTSD and addiction.

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