Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis

Li, Nan-Xi; Hu, Yiru; Chen, Wang-Ni; Zhang, Bin

doi:10.1016/j.jad.2021.09.041

Cited by 41 publications

(33 citation statements)

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“…Over the last decade, there have been a series of clinical trials evaluating the efficacy of psychedelics for treatment of major depressive disorder (MDD) and treatment resistant depression (TRD) (Table 1 ). The results of these trials are summarized in multiple systematic reviews and meta-analysis and thus will be discussed only briefly in this review (Andersen et al 2021 ; Galvao-Coelho et al 2021 ; Kuypers 2021 ; Li et al 2022 ).The efficacy of psilocybin in the form of psychedelic-assisted psychotherapy (PAP) has been evaluated under several clinical trial types, including open label and double blind crossover, and has shown promise at reducing depressive symptoms across all clinical trials (Table 1 ; for a review see (Kuypers 2021 ). Overall, PAP with high hallucinogenic doses (10–30 mg/70 kg) of psilocybin given once or twice on two separate sessions showed remarkable antidepressant effects.…”

Section: The Antidepressant Action Of Psychedelicsmentioning

confidence: 99%

How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

et al. 2022

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Rationale Recent trials with psychedelics in major depressive disorder and treatment-resistant depression showed remarkable improvements in depressive symptoms that can last for up to several months after even a single administration. The lack of an appropriate placebo control group—as patients are often able to discriminate the subjective effects of the drug—and an incomplete understanding of the role of the hallucinogenic and mystical experience, hampers the interpretation of these therapeutic effects. Objectives To control for these factors, we developed a translational framework based on establishing pharmacokinetic/pharmacodynamic (PK/PD) relationships in rodents and humans for hallucinogenic (i.e., discriminative stimulus effects in rodents and humans; head twitch responses in rodents; questionnaires in humans) and therapeutic effects. For the latter, we selected the pattern separation and attentional set-shifting tasks as measures for cognitive flexibility because of their high translational value. We predict that these PK/PD analyses will lead to a more objective evaluation of improvements in patients compared to relying only on the currently used self-reported questionnaires. We hypothesize that—if the role of the hallucinogenic experience is not central in the antidepressant effects of psychedelics—the ED50’s for the therapeutic effects will be significantly lower than for the hallucinogenic and mystical effects. Conclusion Our framework will help to inform future studies that aim at the elucidation of the mechanism(s) of action of psychedelics in depression, and the role of the acute subjective and/or hallucinogenic experience in their effects.

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Section: The Antidepressant Action Of Psychedelicsmentioning

confidence: 99%

How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

et al. 2022

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“…The second psilocybin-specific systematic review examines the efficacy of the drug at various doses in treating cancer-induced depression (which was termed secondary depression) or major depressive disorder (termed primary depression) [ 75 ]. After filtering 1,044 publications, the study focuses on five phase two clinical trials with quantitative meta-analysis; four are randomized control trials and one is an open-label trial.…”

Section: Reviewmentioning

confidence: 99%

“…Presently, this is the most rigorous analysis of the available psilocybin clinical trial data using the high standards of a systematic review. The authors concluded the current evidence suggests that psilocybin may rapidly improve the symptoms of depression in the studied population, and called for further research [ 75 ].…”

Section: Reviewmentioning

confidence: 99%

Unraveling the Mysteries of Mental Illness With Psilocybin

Sotille¹,

Singh²,

Weisman³

et al. 2022

Cureus

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Current medications have not been effective in reducing the prevalence of mental illness worldwide. The prevalence of illnesses such as treatment-resistant depression has increased despite the widespread use of a broad set of psychopharmaceuticals. Transcranial magnetic stimulation and ketamine therapy are making great strides in improving treatment-resistant depression outcomes but they have limitations. New psychotherapeutics are required that specifically target the underlying cellular pathologies leading to neuronal atrophy. This neuronal atrophy model is supplanting the long-held neurotransmitter deficit hypothesis to explain mental illness. Interest in psychedelics as therapeutic molecules to treat mental illness is experiencing a 21st-century reawakening that is on the cusp of a transformation. Psilocybin is a pro-drug, found in various naturally occurring mushrooms, that is dephosphorylated to produce psilocin, a classic tryptamine psychedelic functional as a 5-hydroxytryptamine 2A receptor agonist. We have focused this review to include studies in the last two years that suggest psilocybin promotes neuronal plasticity, which may lead to changes in brain network connectivity. Recent advancements in clinical trials using pure psilocybin in therapy suggest that it may effectively relieve the symptoms of depression in patients diagnosed with major depressive disorder and treatment-resistant depression. Sophisticated cellular and molecular experiments at the systems level have produced evidence that demonstrates psilocybin promotes neuritogenesis in the mouse brain - a mechanism that may address the root cause of depression at the cellular level. Finally, studies with psilocybin therapy for major depressive disorder suggest that this ancient molecule can promote functionally connected intrinsic networks in the human brain, resulting in durable improvements in the severity of depressive symptoms. Although further research is necessary, the prospect of using psilocybin for the treatment of mental illness is an enticing possibility.

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“…Psilocybin (O-phosphoryl-4-hydroxy-N, N-dimethyltryptamine) can be found in many species of psychoactive fungi and is classified as a classical serotoninergic psychedelic drug, which acts as an agonist at serotonin 5-HT2A/C and 5-HT1A receptors [ 1 ]. Psilocybin has recently received a great deal of attention as a potential therapeutic candidate in several neuropsychiatric disorders, especially in treating depression and anxiety [ 2 , 3 ]. However, the acute effects of psilocybin are reflected in altered states of consciousness (characterized by changes in perception (e.g., illusions or pseudo-hallucinations)) and altered sense of self, thinking and emotion that depend on the dosage and several individual nonpharmacological variables [ 4 ] that are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Psilocybin—Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

Viktorin

Griškova-Bulanova

Voicikas

et al. 2022

JPM

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Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to generate gamma activity. Based on previous literature, we studied the impact of psilocybin on 40 Hz ASSR in healthy volunteers. The study was double blind and placebo controlled with a crossover design. A sample of 20 healthy subjects (10M/10F) received psilocybin orally 0.26 mg/kg or placebo. Participants were measured four times in total, one time before ingestion of psilocybin/placebo and one time after ingestion, during the peak of intoxication. A series of 500 ms click trains were used for stimulation. Psilocybin induced a psychedelic effect and decreased 40 Hz ASSR phase-locking index compared to placebo. The extent of the attenuation was related to Cognition and Affect on the Hallucinogen Rating Scale. The current study shows that psilocybin lowers the synchronization level and the amplitude of 40 Hz auditory steady-state responses, which yields further support for the role of gamma oscillations in cognitive processing and its disturbance.

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Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis

Cited by 41 publications

References 50 publications

How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

Unraveling the Mysteries of Mental Illness With Psilocybin

Psilocybin—Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

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