Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

The recent renaissance of psychedelic science has reignited interest in the similarity of drug-induced experiences to those more commonly observed in psychiatric contexts such as the schizophrenia-spectrum. This report from a multidisciplinary working group of the International Consortium on Hallucinations Research (ICHR) addresses this issue, putting special emphasis on hallucinatory experiences. We review evidence collected at different scales of understanding, from pharmacology to brain-imaging, phenomenology and anthropology, highlighting similarities and differences between hallucinations under psychedelics and in the schizophrenia-spectrum disorders. Finally, we attempt to integrate these findings using computational approaches and conclude with recommendations for future research

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity

Coupled free-carrier and exciton relaxation in optically excited semiconductors

The energy relaxation of coupled free-carrier and exciton populations in semiconductors after low-density ultrafast optical excitation is studied through a kinetic approach. The set of semiclassical Boltzmann equations, usually written for electron and hole populations only, is complemented by an additional equation for the exciton distribution. The equations are coupled by reaction terms describing phonon-mediated exciton binding and dissociation. All the other relevant scattering mechanisms, such as carrier-carrier, carrier-phonon, and exciton-phonon interactions, are also included. The resulting system of rate equations in reciprocal space is solved by an extended ensemble Monte Carlo method. As a first application, we show results for the dynamics of bulk GaAs in the range from 1 to ∼200 ps after photoexcitation. The build-up of an exciton population and its sensitivity to the excitation conditions are discussed in detail. As a consequence of the pronounced energy dependence of the LO-phonon-assisted transition probabilities between free-pair states and excitons, it is found that the efficiency of the exciton-formation process and the temporal evolution of the resulting population are sensitive to the excitation energy. We discuss the effects on luminescence experiments

LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality

Lysergic acid diethylamide (LSD) is used recreationally and has been evaluated as an adjunct to psychotherapy to treat anxiety in patients with life-threatening illness. LSD is well-known to induce perceptual alterations, but unknown is whether LSD alters emotional processing in ways that can support psychotherapy. We investigated the acute effects of LSD on emotional processing using the Face Emotion Recognition Task (FERT) and Multifaceted Empathy Test (MET). The effects of LSD on social behavior were tested using the Social Value Orientation (SVO) test. Two similar placebo-controlled, double-blind, random-order, crossover studies were conducted using 100 μg LSD in 24 subjects and 200 μg LSD in 16 subjects. All of the subjects were healthy and mostly hallucinogen-naive 25- to 65-year-old volunteers (20 men, 20 women). LSD produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy on the MET, and impaired the recognition of sad and fearful faces on the FERT. LSD enhanced the participants' desire to be with other people and increased their prosocial behavior on the SVO test. These effects of LSD on emotion processing and sociality may be useful for LSD-assisted psychotherapy

Monte Carlo simulation of ultrafast processes in photoexcited semiconductors: Coherent and incoherent dynamics

The ultrafast dynamics of photoexcited carriers in a semiconductor is investigated by using a Monte Carlo simulation. In addition to a ‘‘conventional’’ Monte Carlo simulation, the coherence of the external light field and the resulting coherence in the carrier system are fully taken into account. This allows us to treat the correct time dependence of the generation process showing a time-dependent linewidth associated with a recombination from states off resonance due to stimulated emission. The subsequent dephasing of the carriers due to scattering processes is analyzed. In addition, the simulation contains the carrier-carrier interaction in Hartree-Fock approximation giving rise to a band-gap renormalization and excitonic effects which cannot be treated in a conventional Monte Carlo simulation where polarization effects are neglected. Thus the approach presents a unified numerical method for the investigation of phenomena occurring close to the band gap and those typical for the energy relaxation of hot carriers

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Prediction of Psilocybin Response in Healthy Volunteers

Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin

ULTRAFAST WAVE PACKET DYNAMICS IN JAHN-TELLER SURFACES; Ag ATOMS TN Xe CRYSTALS

Author Institution: Fachbereich physik, FU BerlinThe dynamics on Jahn-Teller surfaces involving pseudorotation, radial oscillations and the symmetric breathing mode has been already explored in isolated triatomics like $Na_{3}$. This contribution deals with the additional effects occuring in the condensed phase and originating from the energy dissipation to the lattice by phonon emission. A study with femtosecond pump-probe spectroscopy is carried out for substitutional Ag atoms in a rare gas lattice (Xe) of cubic (fcc) symmetry. Excitation from the electronic ground state with s-symmetry to the p-orbitals of the Ag atom leads to a dynamic Jahn-Teller splitting which removes the degeneracy of the p-orbitals by a coupling to nontotally symmetric phonon modes. Energy dissipation of the initially pseudorotating wave packets leads to structural relaxation and to a thermalized population in a strongly statically deformed geometry according to the large Stokes shift of about 2 eV. The initial population in the Jahn-Teller state is probed by a transient bleaching of the ground state resulting in a life time of several ps. The observed subpicosecond dynamics is related to the cubic and noncubic modes derived from MCD experiments. The subsequent energy dissipation of about 0.4 eV corresponding to 80 phonons is detected by fluorescence dip spectroscopy. The static deformation and the thermalization in it is completed in 5-7 ps. This very fast energy relaxation cannot be attributed to single phonon emission events for a phonon period of about 1 ps and is discussed with respect to higher order terms in Jahn-Teller surfaces