Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Historic psychedelic drug trials and the treatment of anxiety disorders.

INTRODUCTION: In this paper, we systematically review literature from 1940 to 2000 relating to the combined use of psychological therapies and psychedelic drugs in the treatment of ICD-10 anxiety disorders. METHODS: The databases Ovid MEDLINE(R), PsycINFO, and Multidisciplinary Association for Psychedelic Studies (MAPS) were searched for case reports and trials involving humans in the treatment of ICD-10 anxiety and related disorders. Twenty-four studies are described; four describe anxiety symptoms in diverse patient groups, 14 studies describe historic diagnoses that usefully correspond with ICD-10 anxiety disorders, six studies pooled results or failed to detail results specific to contemporary ICD-10 anxiety disorders. Two of the 24 studies reported are individual case reports while two of them were inadequate in terms of the reporting of outcome measures. Thus 20 studies were ultimately included in the summary analysis. RESULTS: Three of the 20 studies reviewed described improvements in anxiety by standardized measures (p < .05) and two studies found that this effect was dose related. Of the 20 studies included in the final analysis, 94 of 145 (65%) cases of "psychoneurotic anxiety reaction" as defined by Diagnostic and Statistical Manual of Mental Disorders-I showed improvement that ranged from moderate improvement to full recovery. Despite methodological inadequacies, the results from previous studies are encouraging and should be used to guide and inform further investigation. CONCLUSION: The majority of studies indicate that a combination of psychedelic drug administration and psychological therapy was most beneficial. We found no study suggesting that the pharmacological action of psychedelic drugs in isolation is sufficient.

Pain modulation by illusory body rotation: A new way to disclose the interaction between the vestibular system and pain processing.

BACKGROUND: Clinical and experimental evidence advocates a structural and functional link between the vestibular and other sensory systems. For instance, visuo-vestibular and vestibular-somatosensory interactions have been widely reported. However, whether visual inputs carrying vestibular information can modulate pain is not yet clear. Recent evidence using natural vestibular stimulation or moving visual stimuli, points at an unspecific effect of distraction. METHODS: By using immersive virtual reality (VR), we created a new way to prompt the vestibular system through the vision of static visual cues, studying the possible interaction with pain. Twenty-four healthy participants were visually immersed in a virtual room which could appear with five different degrees of rotation in the sagittal axis, either towards the right, left or with no rotation. Participants' heat pain thresholds and subjective reports of perceived body rotation, sense of presence and attention were measured. RESULTS: 'Being' in a tilted room induced the sensation of body rotation in our participants, even though they were always in an upright position. We also found that rotating the visual scenario can modulate the participants' pain thresholds, determining a significant increase when a left tilt is displayed. In addition, a positive correlation between the perceived body midline rotation and pain threshold was found when the virtual room was titled 15 degrees toward the left. Importantly, all VR conditions were found to be equally distractive. CONCLUSIONS: Vestibular information present in static visual cues can modulate experimentally-induced acute pain according to a side-dependent manner and bypassing supramodal attentional mechanisms. These findings may help refining pain management approaches based on multimodal stimulation. SIGNIFICANCE: This study explored how the visualization of static environments in immersive virtual reality can lead to pain threshold modulation through the activation of the vestibular system. Immersion into rotated virtual environments led to the illusory sensation of body rotation, and this sensation was found to be related with a modulation of pain perception. Possible analgesic effects due to distraction could be ruled out. These results expand our current knowledge about how the visual, vestibular and somatosensory (pain) systems interact. These findings may influence future pain treatment strategies based on multisensory stimulation.