Effects of psilocybin therapy on personality structure.

OBJECTIVE: To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (TRD). METHOD: Twenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3-month follow-up using the Revised NEO Personality Inventory (NEO-PI-R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS-SR16. RESULTS: Neuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO-PI-R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend-level increases, and Agreeableness did not change. CONCLUSION: Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.

LSD-induced entropic brain activity predicts subsequent personality change.

Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc.

The paradoxical psychological effects of lysergic acid diethylamide (LSD).

BACKGROUND: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. METHOD: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. RESULTS: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. CONCLUSIONS: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.

The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories.

3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.

Psychedelics and connectedness.

Psychedelic drugs are creating ripples in psychiatry as evidence accumulates of their therapeutic potential. An important question remains unresolved however: how are psychedelics effective? We propose that a sense of connectedness is key, provide some preliminary evidence to support this, and suggest a roadmap for testing it further.

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.

RATIONALE: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. OBJECTIVES: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. METHODS: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. RESULTS: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. CONCLUSIONS: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.

LSD enhances suggestibility in healthy volunteers.

RATIONALE: Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control. OBJECTIVES: The present study sought to test the effect of LSD on suggestibility in a modern research study. METHODS: Ten healthy volunteers were administered with intravenous (i.v.) LSD (40-80 µg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for 'efficacy' (i.e. A ≈ B) and counterbalanced across conditions (i.e. 50 % completed version 'A' under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects. RESULTS: Volunteers gave significantly higher ratings for the CIS (p = 0.018), but not the MIT (p = 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (p = 0.0005). CONCLUSIONS: These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.

LSD enhances the emotional response to music.

RATIONALE: There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study. OBJECTIVES: The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD. METHODS: Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9). RESULTS: Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness". CONCLUSIONS: These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.