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Journal articleSiegel JS, Subramanian S, Perry D, et al., 2024,
Psilocybin desynchronizes the human brain.
, Nature, Vol: 632, Pages: 131-138A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.
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Journal articleBrouwer A, Carhart-Harris RL, Raison CL, 2024,
Psychotomimetic compensation versus sensitization.
, Pharmacol Res Perspect, Vol: 12It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.
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Journal articleLynskey MT, Thurgur H, Athanasiou-Fragkouli A, et al., 2024,
Suicidal Ideation in Medicinal Cannabis Patients: A 12-Month Prospective Study.
, Arch Suicide Res, Pages: 1-15OBJECTIVE: To document the prevalence and correlates of suicidal ideation (SI) among individuals seeking cannabis-based medicinal products (CBMPs); to test whether SI declines or intensifies after three months of CBMP treatment and to document 12-month trajectories of depression in those reporting SI and other patients. METHOD: Observational data were available for 3781 patients at entry to treatment, 2112 at three months and 777 for 12 months. Self-reported depressed mood and SI were assessed using items from the PHQ-9. Additional data included sociodemographic characteristics and self-reported well-being. RESULTS: 25% of the sample reported SI at treatment entry and those with SI had higher levels of depressed mood (mean = 17.4 vs. 11.3; F(1,3533) = 716.5, p < .001) and disturbed sleep (mean = 13.8 vs. 12.2, F(1,3533) = 125.9, p < .001), poorer general health (mean = 43.6 vs. 52.2, F(1,3533) = 118.3, p < .001) and lower quality of life (mean = 0.44 vs. 0.56 (F(1,3533) = 118.3, p < .001). The prevalence of SI reduced from 23.6% to 17.6% (z = 6.5, p < .001) at 3 months. Twelve-month follow-up indicated a substantial reduction in depressed mood with this reduction being more pronounced in those reporting SI (mean (baseline) = 17.7 vs. mean (12 months) = 10.3) than in other patients (mean (baseline) = 11.1 vs. mean (12 months) = 7.0). CONCLUSIONS: SI is common among individuals seeking CBMPs to treat a range of chronic conditions and is associated with higher levels of depressed mood and poorer quality of life. Treatment with CBMPs reduced the prevalence and intensity of suicidal ideation.
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Journal articlede la Salle S, Kettner H, Thibault Lévesque J, et al., 2024,
Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy.
, Sci Rep, Vol: 14Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these 'real-world' patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.
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Journal articleThurgur H, Lynskey M, Schlag AK, et al., 2024,
Authors' response to letter 'On the use of open-label studies for the evaluation of cannabis-based products for the treatment of long-COVID'.
, Br J Clin Pharmacol -
Journal articleRoseman L, Erritzoe D, Nutt D, et al., 2024,
Interrupting the Psychedelic Experience Through Contextual Manipulation to Study Experience Efficacy.
, JAMA Netw Open, Vol: 7 -
Journal articleBornemann J, Close JB, Ahmad K, et al., 2024,
Study protocol for “Psilocybin in patients with fibromyalgia: brain biomarkers of action”
, Frontiers in Psychiatry, Vol: 15, ISSN: 1664-0640Background: Chronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI).Methods: Twenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity – plus event-related potential functional plasticity markers, captured via EEG.Discussion: The results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic actio
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Journal articleLynskey MT, Thurgur H, Athanasiou-Fragkouli A, et al., 2024,
Prescribed Medical Cannabis Use Among Older Individuals: Patient Characteristics and Improvements in Well-Being: Findings from T21
, DRUGS & AGING, Vol: 41, Pages: 521-530, ISSN: 1170-229X -
Journal articleIzmi N, Kettner H, Carhart-Harris R, et al., 2024,
Psychological effects of psychedelics in adolescents
, Frontiers in Child and Adolescent Psychiatry, ISSN: 2813-4540This study aimed to investigate differences in long-term psychological effects, acute subjective effects, and side effects associated with psychedelic use in adolescents (aged 16-24), compared with adults (aged 25+). Data from two observational online survey cohorts was pooled, involving adolescents (average age 20.4 ± 2.2, N=435) and adults (average age 36.5 ± 9.7, range = 25-71,N=654) who self-initiated a psychedelic experience and were tracked via online surveys from a pre-experience baseline to four weeks post-use. Self-reported measures of well-being were collected one week before, and two and four weeks after psychedelic use. Acute subjective drug effects, dosage and contextual variables pertaining to the setting of use were measured on the day after the session. Repeated-measures analyses of covariance, t-and z-tests, as well as exploratory correlational and regression analyses tested differences in psychological changes, acute drug effects, and side effects between the two groups. Psychological well-being significantly improved in adolescents two and four weeks following psychedelic use, with a clinically relevant mean change score of 3.3 points (95% CI: 1.1 ‐5.5). on the Warwick‐Edinburgh Mental Wellbeing Scale [F(1.8, 172.9)=13.41, η 2 G=.04, p<.001], statistically indistinguishable from changes in adults. Acute subjective effects differed between the age groups; adolescents reported significantly higher challenging experiences and ego-dissolution. In adolescents, visual symptoms related to 'hallucinogenpersisting perceptual disorder' (HPPD) were reported at a higher prevalence than in adults (73.5 % vs 34.2 %, p<.001) but were reported as distressing by only one adolescent participant. To our knowledge, this is the first prospective study to examine the psychological effects of psychedelic use specifically in adolescents. Statistically significant improvements in psychological well-being and other domains of mental health were obse
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Journal articleNutt D, Crome I, Young AH, 2024,
Is it now time to prepare psychiatry for a psychedelic future?
, BRITISH JOURNAL OF PSYCHIATRY, ISSN: 0007-1250
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