Neuroscience & Biobehavioral Reviews
May 21, 2022
Vince Polito, Paul Liknaitzky
110 citations
A systematic review of 44 studies on microdosing psychedelics, published between 1955 and 2021, finds that laboratory studies show changes in pain perception, time perception, conscious state, and neurophysiology, while self-report studies indicate changes in cognitive processing and mental health. The studies varied widely in risk of bias. The authors argue that claims attributing microdosing effects largely to expectancy are premature and possibly wrong. They also clarify definitional inconsistencies by suggesting dose ranges for different substances and provide design suggestions for more rigorous future research.
Australian & New Zealand Journal of Psychiatry
March 21, 2021
Daniel Perkins, Jerome Sarris, Susan L. Rossell et al.
53 citations
Psychedelic substances such as psilocybin, ayahuasca, LSD, and MDMA are gaining renewed medical interest due to the need for new psychiatric treatments and promising study results. This viewpoint reflects on the Royal Australian and New Zealand College of Psychiatrists' Clinical Memorandum on Psychedelics and notes regulatory developments, including applications for down-scheduling and access approvals. The authors argue that rigorous research is needed to assess benefits, safety, and therapeutic mechanisms. They summarize recent findings on mechanisms of action and the psychedelic-assisted psychotherapy model, suggesting medicinal psychedelics could become a new class of psychiatric treatments when used under medical supervision with psychotherapeutic support. However, sufficiently powered trials and safety protocols are required before clinical use, and untrained practitioner access could be harmful.
Frontiers in Neuroscience
February 4, 2020
Claire J. Foldi, Paul Liknaitzky, M.l. Williams et al.
52 citations
Anorexia nervosa has the highest mortality rate of any psychiatric disease, and current medications are largely ineffective partly because the neurobiological drivers are poorly understood. Recent research into psychedelic medicine suggests psilocybin may alleviate symptoms related to serotonin signaling and cognitive inflexibility. Clinical trials for treatment-resistant depression show promise but have methodological biases. The first clinical trial using psilocybin for anorexia nervosa began in 2019, highlighting the need to understand the neurobiological mechanisms. Animal models, such as the activity-based anorexia rodent model, allow detailed study of brain function and behavior without the confounds of expectancy and bias, and are argued to be crucial for informing which patient subpopulations may benefit most from psychedelic medicine.
Frontiers in Psychiatry
November 4, 2021
M.l. Williams, Diana Korevaar, Renee Harvey et al.
23 citations
After a 40-year research hiatus due to sociopolitical issues, psychedelic-assisted therapies are being reinvestigated for mental illness. Clinicians and researchers in Australia identified five categories of challenge to moving these therapies from clinical trials to community practice: inherent risks, poor clinical practice, inadequate infrastructure, problematic perceptions, and divisive relationships. They propose strategies including public-sector support for research and training to establish best practices, funding for equitable access, and a multidisciplinary advisory body to guide policy. While framed in Australia, the challenges and strategies may apply elsewhere.
Australian & New Zealand Journal of Psychiatry
November 22, 2019
Sally Meikle, Paul Liknaitzky, Susan L. Rossell et al.
19 citations
Psilocybin, a psychedelic drug, is gaining attention as a potential treatment for depression due to its mechanism of action, benefits in early trials, and relatively low side effect burden. This viewpoint outlines key unresolved issues for its clinical use: identifying which patients are most likely to benefit or experience adverse effects, understanding longer-term outcomes, and clarifying the role of psychotherapeutic support alongside the drug. There are also opportunities to better understand the neurobiology underlying its effects.
Journal of Psychopharmacology
June 14, 2024
Vince Polito, Paul Liknaitzky
16 citations
A rapid review of 19 placebo-controlled studies found that microdosing with LSD and psilocybin produces changes in neurobiology, physiology, subjective experience, affect, and cognition compared to placebo. The authors argue that claims microdosing is mostly a placebo are premature and possibly wrong, citing eight reasons: few controlled studies, small sample sizes, evidence of dose-dependent effects, limited dose ranges tested, possibly too-small doses, non-clinical populations only, selection bias, and small measured impact of expectancy. They conclude it is not yet possible to determine whether microdosing is a placebo.
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.
Neuroscience and biobehavioral reviews
June 1, 2025
Joshua Kugel, Ruben E Laukkonen, David B Yaden et al.
15 citations
A sudden shift in understanding or perspective that feels true—called insight—is common during psychedelic experiences and is often considered central to their therapeutic value. A systematic review of 98 studies (40 survey, 58 interventional) found that insight was positively correlated with psychedelic dose and was significantly higher after psychedelics in 93% of studies comparing to placebo. Crucially, 86% of studies found that insight was associated with therapeutic improvement, and this relationship was often stronger than that of mystical-type experience. The findings suggest insight's importance for clinical practice and understanding mechanisms of psychedelic therapy, though heterogeneous study designs and possible publication bias limit meta-analytic conclusions.
Drug and Alcohol Review
November 5, 2024
Jordan J Negrine, Cheneal Puljević, Jason Ferris et al.
8 citations
Australian psychologists generally hold positive attitudes toward psychedelic-assisted therapy (PAT) following the 2023 regulatory changes that permitted psilocybin and MDMA in clinical services. Most view PAT as promising for chronic mental health conditions like depression, but express concerns about limited evidence on efficacy, potential adverse experiences, and the complexity of individualized treatment protocols. Many psychologists lack detailed knowledge about the interventions. The findings emphasize the need for comprehensive education and training programs, including exposure to psychedelic experiences and credible higher education institutions, to ensure competent administration of PAT.
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.
Journal of Applied Sport Psychology
November 10, 2020
Courtney C. Walton, Paul Liknaitzky
6 citations
Classical psychedelics such as LSD, psilocybin, and DMT are being revisited in clinical research and show promise for improving well-being and reducing mental ill-health with a good safety profile. Elite athletes experience mental health problems at rates similar to or higher than the general population. Psychedelic treatment may help athletes with issues like therapeutic resistance, identity challenges during career transitions or injury, and interpersonal stress. As these treatments advance toward regulatory approval in the US and EU, it is timely to consider their application in elite sport. The article outlines sport-specific relevance, the roles of sports psychologists and psychiatrists, ethical and regulatory issues, and proposes initial research questions, arguing that psychedelic-assisted psychotherapy should be investigated as a novel treatment for mental ill-health in elite athletes.
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.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Sally Meikle, Olivia Carter, Paul Liknaitzky et al.
2 citations
In an open-label pilot trial, two 25 mg doses of psilocybin combined with psychotherapy produced a clinically meaningful reduction in depressive symptoms at 3 weeks in people with treatment-resistant depression. The average improvement was sustained at 20 weeks, but individual responses varied: two participants showed lasting benefit, three relapsed, and two did not improve. Mindset before dosing, spiritual experiences, and perceptual changes during the session predicted treatment trajectory, whereas treatment expectations did not. No serious adverse events occurred. The findings support further research into tailoring psilocybin therapy to individual variability.
June 4, 2023
Vince Polito, Paul Liknaitzky
2 citations
preprint
Claims that microdosing psychedelics works only through placebo effects are premature and possibly wrong, based on eight shortcomings in the existing evidence from dose-controlled studies of low-dose LSD and psilocybin. Only a small number of controlled studies exist, most with small sample sizes. There is some evidence of dose-dependent effects, but only a few doses have been tested, and those may have been too low. Studies have examined only non-clinical populations and have been susceptible to selection bias, while the measured impact of expectancy itself is small. Given these limitations, it is not yet possible to determine whether microdosing is a placebo.
December 15, 2021
Vince Polito, Paul Liknaitzky
2 citations
preprint
A systematic review of 44 studies on microdosing psychedelics, published between 1955 and 2021, found changes in pain perception, time perception, conscious state, and neurophysiology in laboratory studies, and changes in cognitive processing and mental health in self-report studies. The review argues that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. It also provides suggested dose ranges to clarify definitional inconsistencies and offers design suggestions for more rigorous future research.
Brain and behavior
February 1, 2026
Rachel Ham, John Gardner, Adrian Carter et al.
1 citation
In psilocybin-assisted therapy, therapeutic touch can foster emotional connection, provide grounding during intense experiences, and modulate the depth of the psychedelic state, but its acceptability depends on the quality of the therapeutic relationship and robust consent processes. Most participants valued having touch available, especially after firsthand experience, and several attributed therapeutic benefit directly to touch. However, some also identified potential for discomfort or distraction, highlighting the need for sensitivity to individual history and context. The findings underscore the importance of explicit preparation, consent, and attunement when incorporating touch into psychedelic therapy.
Psychoactives
March 25, 2024
Agnieszka D. Sekula, Prashanth Puspanathan, Luke A. Downey et al.
1 citation
A review of three interventions that produce altered states of consciousness—psychedelic-assisted psychotherapy, Transcendental Meditation, and hypnotherapy—finds that the first two are linked to significant reductions in substance misuse and improvements in emotional, cognitive, and social functioning, motivation, self-identity, and meaning. Hypnotherapy, despite wider acceptance, shows mixed and minimal results for substance misuse treatment. The review notes common phenomenological, psychological, and neurobiological features among the interventions, suggesting possible convergent mechanisms, but also highlights mixed findings and methodological issues. Key research gaps and promising future directions are outlined.
Research square
May 19, 2026
Sunjuri Sun, Claudia Hanson, Peter S Hendricks et al.
The evidence on child and maternal outcomes after exposure to classic psychedelics during pregnancy is very sparse and of very low certainty. A systematic review of 42 studies, mostly case reports from high-income countries, found that LSD was the most commonly reported substance. Outcomes reported included spontaneous abortions (2 studies), stillbirth (1 study), neonatal mortality (16 studies), preterm birth (17 studies), birthweight (15 studies), and congenital malformations (26 studies). No maternal deaths were reported. Because of small sample sizes and varied study designs, no meta-analysis was possible. The authors conclude that methodologically rigorous research on psychedelic use during pregnancy is urgently needed.
medRxiv
November 17, 2025
Georgia Ioakimidis-Macdougall, John Gardner, Paul Liknaitzky
preprint
A single 25 mg dose of psilocybin, given with psychological support in a clinical setting, helped 14 mental health professionals develop a greater embodied understanding of therapeutic principles and processes. Participants reported increases in empathy, attunement, and emotion regulation—qualities that underpin therapeutic alliance and promote trust and safety. While no harms were reported, participants noted two potential risks: the experience could feel destabilizing, and therapists might project their own experience onto clients, narrowing interpretative range. Participants indicated that such training is necessary but not sufficient for high-quality psychedelic-assisted therapy. Findings support including an optional psychedelic experiential component for clinicians with prior training and reflective capacity.
The International Journal of Neuropsychopharmacology
August 1, 2025
Andrew S. Gibbons, Paul Liknaitzky, Suresh Sundram
Generalised Anxiety Disorder (GAD) is often treated with psilocybin-assisted therapy (PAT), but only about 44% of participants respond. This multi-omic study compared blood samples from 11 responders and 13 non-responders after a 6-week PAT regime. Five genes were differentially expressed between groups, including CTXN2-AS1 and HLA-V. A panel of four genes (CTXN2-AS1, DUT-AS1, HLA-V, and PARP16) could distinguish 45% of responders from all other participants. These findings suggest potential blood biomarkers for predicting PAT response in GAD, though validation in larger cohorts is needed.
The International Journal of Neuropsychopharmacology
August 1, 2025
Susan Meikle, Olivia Carter, Paul Liknaitzky et al.
A small pilot trial of psilocybin with psychotherapy for treatment-resistant depression found a clinically meaningful reduction in depressive symptoms three weeks after the second dose, with an average improvement of 7.14 points on the depression scale and a large effect size. However, individual responses varied widely: two participants showed lasting improvement, three relapsed, and two saw no substantial benefit. Mindset before dosing and spiritual or perceptual experiences during the session predicted treatment trajectory, but prior expectations did not. The study supports further research into tailoring psychedelic therapy to individual differences.
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.
March 21, 2025
R. Ham, John Gardner, Adrian Carter et al.
preprint
In a clinical trial of psilocybin-assisted therapy for generalized anxiety disorder, 18 participants provided longitudinal perspectives on therapeutic touch. Most valued touch, especially after experiencing it during psilocybin dosing sessions. Touch offered connection during intense emotions and could manage the intensity of acute psychedelic experiences. Some attributed direct therapeutic effects to touch, and a strong therapeutic relationship was essential for its effective use. The authors argue that touch application should be individualized and embedded in comprehensive consent, with further research needed on safety and therapist training.
Therapeutic advances in psychopharmacology
January 1, 2025
Diana McHerron, Michaela Barber, Rachel Ham et al.
Physical touch is often used as a supportive tool in psychedelic-assisted therapy, but participants under the influence of psychedelics have reduced capacity to consent and are more suggestible. Interviews with 16 researchers revealed three themes: flexible frameworks, therapeutic alliance, and boundary management. Researchers noted that consent to therapeutic touch should be established before dosing sessions and continually managed. Flexibility in consent protocols helped build therapeutic alliance but also created challenges in boundary management. Researchers emphasized the need for clearer ethical guidelines for handling changing preferences during dosing sessions and limits on expanding consent after drug administration.
Focus (American Psychiatric Publishing)
July 1, 2024
Claire J Foldi, Paul Liknaitzky, Martin Williams et al.
Anorexia nervosa has the highest death rate of any psychiatric illness, but current medications are largely ineffective partly because the neurobiological causes are poorly understood. Renewed research into psychedelic medicine, particularly psilocybin, suggests it may help symptoms related to serotonin signaling and cognitive inflexibility in anorexia nervosa. Clinical trials for treatment-resistant depression show promising results, though methodological biases remain. The first clinical trial of psilocybin in anorexia nervosa patients began in 2019, highlighting the need to understand the underlying neurobiological mechanisms. Animal models, such as the activity-based anorexia rodent model, can provide detailed brain and behavior analysis without the confounds of patient expectancy and bias. The authors argue such studies are crucial for informing clinical applications and identifying which patient subpopulations might benefit most.