Imported Top List

In depression and other neuropsychiatric disorders, degradation of neurons and loss of dendritic spines is a common marker. Some studies on ketamine and serotonergic psychedelics suggest that these substances promote neuronal growth and the strengthening of synaptic responses by promoting plasticity. This study by Ly and colleagues (2018) demonstrated a robust psychoplastogenic response to DMT, psilocin, MDMA, DOI, and LSD in rodents. The effect was inhibited, in a dose-dependent fashion by increasing the ketanserin concentration, which is an antagonist of 5-HT2A receptors. These results suggest that psychedelics mediate structural plasticity by increasing the density of dendritic spines on cortical neurons.

The Subjective Drug Intensity (SDI) and the Mystical Experience Questionnaire (MEQ) are often used to measure subjective experiences induced by psychedelics, along with PET scans, which assess 5HT2Ar binding. In the recent study by Stenbaek and colleagues (2020), the SDI was taken every 20 min and MEQ at the end of the session. The data revealed that during the experience after a single dose of psilocybin, the real-time estimate of Subjective Drug Intensity correlated with the percentage of 5HT2Ar occupancy. The authors suggest that “longer peak plateau and a more rapid return to normal waking consciousness, as measured with SDI, are temporal subjective building blocks upon which a more profound mystical experience can unfold.” More research is recommended since the study did not explore individual variability in psilocin pharmacokinetics.

Neuroimaging studies suggest comparable neuronal activation patterns during the REM sleep phase and psychedelic experiences in temporal lobe regions. A common feature investigated by studies on the phenomenological structure of dreaming is termed cognitive bizarreness. It is a strange and irrational quality of dreams, where events, perception, and thoughts are imaginary and improbable. This double-blind study by Kraehenmann and colleagues (2017) measured the cognitive bizarreness scores during a guided mental imagery task in a post-peak LSD-induced state, placebo, and LSD after pre-treatment with ketanserin. The data showed that LSD increased cognitive bizarreness, which was related to the subjective loss of self-boundaries and cognitive control. Ketanserin treatment caused 5HT2Ar inhibition and the failure of the dreamlike effect. These results contributed to the understanding of the basis of dreamlike waking imagery in LSD-induced states, regulated by 5HT2A receptors.

Kraehenmann and colleagues (2017) used a similar double-blind, placebo-controlled study design on LSD with ketanserin as a 5HT2Ar antagonist. In this study, they investigated primary process thinking – an automatic mode of mental organization characterized by image fusions, contradictory and illogical events, feelings, and thoughts, typically occurring during altered states of consciousness (ASCs), for example dreaming. DMN characterizes secondary process thinking which is a higher-level mental activity, based on reflection, adaptability, rationality, and logic. Primary index (PI) was used to measure primary process thinking, and cognitive bizarreness was evaluated from the mental imagery scores as a measure for dream mentation. The results suggested that LSD increases primary process thinking, and the authors proposed that psychedelic states may be hybrid states between waking and dreaming consciousness, induced by 5HT2A receptor activation.

5HT2A receptors are abundantly expressed in the amygdala, where the activity is directly affected by psychedelics. The amygdala is involved in threat-processing and in pathophysiological conditions its hyperactivity might be modulated by 5HT2Ar agonists, leading to antidepressant and anxiolytic (anxiety) effects. This article analysed the data from a previous study of the group, trying to contribute to the growing body of evidence that the effects of psilocybin on threat processing possibly arise from the changes in amygdala connectivity. The data showed that psilocybin (in a placebo-controlled setting) reduces the modulatory effects of visual threats. Furthermore, the researchers suggest a model, where reciprocal connections between the primary visual cortex and amygdala and between the amygdala and lateral prefrontal cortex are critical in regulating negative emotions.

Several studies in this list focused on the universal mechanisms of psychedelic-induced 5HT receptor response. The subjective effects, however, can significantly vary among patients. To understand the individual variability in subjective states, Candace Lewis and colleagues (2020) investigated subjective ratings in sub-scales of the Five-Dimensional Altered State of Consciousness (5D-ASC) with high emotionality in healthy participants who received either a high or a low dose of psilocybin. The group, which included Katrin Preller and Franz Vollenweider, hypothesized that cingulate cortex thickness could predict the subjective psilocybin experience. Indeed, the greater thickness of the anterior cingulate cortex (but not caudal and posterior c.c.), which expresses a high amount of 5HT2A receptors, predicted higher subjective ratings in sub-scales of the 5D-ASC.