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Jonathan Brett

St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.

12 papers in the library · 48 citations · publishing 2023-2026

Papers

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder

Frontiers in Psychiatry March 14, 2023 Jonathan Brett, Elizabeth Knock, Paul Liknaitzky et al. 16 citations

Methamphetamine use disorder is a chronic condition with high relapse rates and limited effective treatments. Contingency management and psychotherapy show modest efficacy, while pharmacological options have little to no benefit. Psilocybin-assisted psychotherapy is emerging as a promising approach for substance use disorders, though no studies have yet examined it for methamphetamine use disorder. This review presents the rationale for using psilocybin-assisted psychotherapy to treat methamphetamine use disorder and describes practical considerations from early experience designing and implementing four clinical trials on this approach.

Drug dependence and prescribing ketamine for treatment-resistant depression in Australia and New Zealand.

The Australian and New Zealand journal of psychiatry October 1, 2024 Alistair Carroll, Adam Bayes, Mark Montebello et al. 10 citations

Ketamine is a restricted medication in Australia and New Zealand, with regulations that vary by jurisdiction and generally limit its use in patients who have a history of drug dependence. There is substantial variation in how drug dependence is defined legally and clinically, with clinical definitions from the ICD-11 and DSM-5. This paper reviews evidence on the risk of ketamine misuse and dependence among patients with a history of illicit drug use, abuse, or dependence, and offers recommendations for psychiatrists prescribing ketamine for treatment-resistant depression in this population.

The psychedelic call: analysis of Australian Poisons Information Centre calls associated with classic psychedelics.

Clinical toxicology (Philadelphia, Pa.) April 1, 2024 Rachael Wilkes, Darren M Roberts, Paul Liknaitzky et al. 8 citations

Calls to the New South Wales Poisons Information Centre about classical psychedelics more than doubled from 45 in 2014 to 105 in 2022, with 737 total calls over nine years. Most calls involved LSD (48%) or psilocybin (47%); 85% came from or were referred to a hospital. Co-ingestion with other substances occurred in 34% of calls. Among single-substance exposures, common clinical features were hallucinations (28%), gastrointestinal symptoms (22%), and tachycardia (18%); seizures occurred in 3%. The increase likely reflects growing community use, possibly driven by interest in psychedelic-assisted therapy trials. Toxicity was relatively high compared to clinical trial safety, which may be due to uncontrolled community use.

Psilocybin-assisted psychotherapy for methamphetamine dependence: a case report involving daily methamphetamine use

Frontiers in Psychiatry December 6, 2024 Jonathan Brett, Elizabeth Knock, Kathy Watson et al. 7 citations

A daily methamphetamine user, a 36-year-old transwoman, achieved sustained abstinence and improved mental health after a single session of psilocybin-assisted psychotherapy following inpatient withdrawal management. She reported increased self-esteem, mindfulness, and distress tolerance over three months. The case suggests that psilocybin-assisted therapy may offer a scalable, safe, and effective approach for treating methamphetamine dependence, though further research is needed to confirm generalizability.

Psilocybin‐assisted psychotherapy for methamphetamine use disorder: A pilot open‐label safety and feasibility study

Addiction September 20, 2025 Elizabeth Knock, Krista J. Siefried, Gillinder Bedi et al. 4 citations

A single 25 mg dose of psilocybin combined with psychotherapy was safely delivered in an outpatient setting to 15 people seeking treatment for methamphetamine use disorder. No serious adverse events occurred; mild side effects included headache, nausea, and noise sensitivity. Methamphetamine use dropped from a median of 12 days in the prior month at screening to 0 days at 28 days and 2 days at 90 days after dosing. Craving decreased while quality of life, depression, anxiety, and stress scores improved at follow-ups. A larger randomized trial is needed to confirm efficacy.

'A fine line between euphoria and death': a qualitative study exploring gamma-hydroxybutyrate (GHB) use among people who identify as heterosexual living in Australia.

Harm reduction journal February 6, 2026 Keaton Hudson-Buhagiar, Jonathan Brett, Alanah Spillane et al. 1 citation

Among heterosexual Australians who use GHB, three patterns of use—occasional, regular, or daily—emerged. Four key themes were identified: escapism (managing mental health symptoms, enhancing confidence, facilitating sex, and alleviating body consciousness in women); diverse understandings of overdose, including intentional dosing to achieve unconsciousness and misconceptions about using stimulants to counter toxicity, with fear of police delaying help-seeking; stigma from both drug-using and non-using peers; and gendered harm reduction practices where women protect each other from harms, especially sexual violence. Findings point to gaps in public health education on overdose management and intentional risk-taking.

Exploring the perceived usefulness of integration support after naturalistic psychedelic experiences in people concerned about their substance use: A survey

Journal of Psychedelic Studies April 22, 2025 Sophie van der Helder, K. Siefried, L. Acheson et al. 1 citation

Most people with substance use concerns who had used psychedelics in the past year thought that psychosocial support after their experiences would be useful. Of 108 participants, 94 (87.0%) considered integration support helpful. Among those interested, most preferred individual support led by a psychologist (67.0%) or a peer worker with lived experience of psychedelic use (58.5%), focusing on applying insights from the psychedelic experience to daily life (63.0%). The findings suggest potential benefits for offering such support and could be explored further with qualitative research.

Protocol of an open-label safety and feasibility pilot study of ketamine-assisted psychotherapy for methamphetamine use disorder (the KAPPA trial).

BMJ open February 10, 2025 Kathryn Fletcher, Nadine Ezard, Krista J Siefried et al. 1 citation

A pilot study will test the safety and feasibility of combining subanaesthetic ketamine with cognitive behavioural therapy for adults with methamphetamine use disorder. Twenty participants seeking to reduce or stop methamphetamine use will receive three subcutaneous ketamine doses (0.75 to 0.9 mg/kg) at weekly intervals and four therapy sessions over four weeks. The study will measure recruitment time, eligibility rates, treatment completion, retention, and acceptability over eight weeks, and explore changes in methamphetamine use, cravings, withdrawal, quality of life, and treatment satisfaction over 24 weeks. No pharmacological treatments currently exist for this condition, and psychotherapy alone is only moderately effective.

Navigating ‘k-land’: a qualitative exploration of participants’ experiences of ketamine-assisted psychotherapy for methamphetamine use disorder

Frontiers in Psychiatry June 24, 2026 Kathryn Fletcher, Nadine Ezard, Krista J. Siefried et al.

People with methamphetamine use disorder who underwent ketamine-assisted psychotherapy described the treatment as a multi-stage process rather than a simple drug effect. Participants reported that ketamine created a temporary state of reduced emotional and cognitive reactivity, which they called 'psychological space,' making them more receptive to psychotherapy. However, behavioral changes—including reduced methamphetamine use—were variable and depended on ongoing therapeutic engagement, personal motivation, and life context. Participants were uncertain whether improvements came from the ketamine, the therapy, or the supportive environment. Acceptability was generally high when treatment occurred in a structured clinical setting.

"Large-Scale and Local Functional Connectivity Changes Following Psilocybin Administration in Methamphetamine Use Disorder.

AJNR. American journal of neuroradiology April 24, 2026 Joga Chaganti, Krista J Siefried, Veda S Vyakaranam et al.

In individuals with methamphetamine use disorder, psilocybin administration alongside psychotherapy led to measurable reorganization of large-scale brain networks and local neural synchrony. After the intervention, connectivity within and between attentional, default mode, and salience networks shifted significantly, and local synchrony increased in frontal and sensorimotor regions. Greater reductions in methamphetamine use correlated with recovery of frontostriatal and attentional connectivity, while reduced psychological distress was linked to strengthened integration of attentional and prefrontal-striatal circuits. These findings suggest psilocybin may promote network-level plasticity in stimulant addiction and support the potential of resting-state fMRI metrics as biomarkers of such change.

A qualitative analysis of participant expectations and experiences of psilocybin‐assisted psychotherapy for methamphetamine use disorder

Addiction December 22, 2025 Jonathan Brett, Toby Lea, Elizabeth Knock et al.

People with methamphetamine use disorder who took part in psilocybin-assisted psychotherapy reported that the treatment was acceptable and often transformative. Before treatment, participants held tempered hopes for positive outcomes. During the psychedelic sessions, many confronted challenging emotional or psychic obstacles by deliberately 'leaning into' them, a process that led to new understandings of themselves, their personal histories, and their relationships. Resolving these obstacles was associated with a reduced importance of methamphetamine in their lives. The therapeutic relationship—characterized by concentrated attention and deep interpersonal intimacy between participant and therapist—was seen as critical to these positive changes.

Exploring psychedelic experiences among people who regularly use methamphetamine: Findings from an international survey.

Drug and alcohol dependence July 1, 2025 Dilara Bahceci, Krista Siefried, Maureen Steele et al.

Among 268 people who used methamphetamine, nearly half had a diagnosed mental illness and were at risk of suicide, and most had taken other substances besides methamphetamine and psychedelics. Most psychedelic experiences were unplanned, recreational, and combined with other drugs. After the experience, about 59% reported improved mood, 50% improved social functioning, and 34% reduced methamphetamine use. Planning the experience and having less challenging experiences were linked to better outcomes. The findings suggest that psychedelic use may improve mood and social function and reduce substance use in this population, but highlight the importance of context and setting.