Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. Th...

https://journals.sagepub.com/doi/pdf/10.1177/0269881116675513

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

https://www.thelancet.com/pdfs/journals/lanpsy/PIIS2215-0366(16)30065-7.pdf

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Background:Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a...

https://journals.sagepub.com/doi/pdf/10.1177/0269881116675512

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

https://www.pnas.org/content/pnas/109/6/2138.full.pdf

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neural dynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of ‘primary states’ is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. It is noted that elevated entropy in this sense, is a characteristic of systems exhibiting ‘self-organised criticality’, i.e., a property of systems that gravitate towards a ‘critical’ point in a transition zone between order and disorder in which certain phenomena such as power-law scaling appear. This implies that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organised activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as REM sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetised state.

/pdf/the-entropic-brain-a-theory-of-conscious-states-informed-by-99bqqui5xr.pdf

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

CONTEXT Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. OBJECTIVE To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. DESIGN A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. SETTING A clinical research unit within a large public sector academic medical center. PARTICIPANTS Twelve adults with advanced-stage cancer and anxiety. MAIN OUTCOME MEASURES In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. RESULTS Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. CONCLUSIONS This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00302744.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/210962/yoa05049_71_78.pdf

Gurpreet S. Chopra

Papers

Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer