Psychopharmacology

Hendricks, P., Copes, H., Family, N., Williams, L. T J., Luke, D., & Raz, S. (2022). Perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide (LSD) in healthy participants within a novel intervention paradigm: Qualitative results from a proof-of-concept study. Journal of Psychopharmacology, 36(3) 337-347. https://doi.org/10.1177/02698811211055855

Background: Classic psychedelics show promise in the treatment of mental health conditions; however, more scalable intervention protocols are needed to maximize access to these novel therapeutics. In this proof-of-concept study, perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide (LSD) were evaluated among healthy participants (N = 31) administered 50 to 100 µg LSD in a treatment paradigm conceptualized as more scalable than traditional approaches to administering classic psychedelics. Methods: Semi-structured interviews assessed participants' expectations, experience, and thoughts on the safety and efficacy of the study design. These interviews were transcribed for thematic analysis relating to perceptions of safety, subjective effects, and beliefs about the clinical utility of LSD. Results: Most participants felt safe throughout the study, with a minority reporting concerns related to having a challenging experience that diminished over time. Participants attributed their feelings of safety to the study structure and support of their attendants, which allowed them to "let go" and immerse themselves in the experience without preoccupation. Furthermore, participants reported transcendent, mystical-type experiences characteristic of classic psychedelics, with almost half highlighting the prominent role played by music during the acute period of drug action. Finally, participants endorsed support for the clinical utility of LSD in controlled environments, expressing the belief that LSD is safe and has the potential to help others. Conclusion: Findings provide preliminary support for the feasibility of this scalable interventional paradigm and set the stage for future critical research with clinical populations.

Michael, P., Luke, D., & Robinson, O. (2021). An encounter with the other: A thematic and content analysis of DMT experiences from a naturalistic field study. Frontiers in Psychology: Consciousness Research, 12, 720717. Doi: 10.3389/fpsyg.2021.720717

Introduction: N,N-dimethyltryptamine (DMT) is an endogenous serotonergic psychedelic capable of producing radical shifts in conscious experience. Increasing trends in its use, as well as new trials administering DMT to patients, indicate the growing importance of a thorough elucidation of the qualitative content, over and above structure, which the drug occasions. This is particularly in light of the hyper-real, otherworldly, and often ontologically challenging yet potentially transformative, nature of the experience, not least encounters with apparently non-self social agents. Laboratory studies have been limited by clinical setting and lacking qualitative analyses of experiential content, while online surveys’ limitations lie in retrospective design, uncontrolled use, and both of which not guaranteeing ‘breakthrough’ experiences, i.e., producing very strong psychoactive effects.

Methods: We report on the first naturalistic field study of DMT use including its qualitative analysis. Screened, healthy, anonymised and experienced DMT users were observed during their non-clinical use of the drug at home (40–75 mg inhaled). In-depth semi-structured interviews (inspired by the micro-phenomenological technique) were employed immediately after their experience. This paper reports on the thematic analysis of one major domain of the breakthrough experiences elicited, the ‘other’. Thirty-six post-DMT experience interviews with mostly Caucasian (83%) males (eight female) of average 37 years were predominantly inductively coded.

Results: Invariably, profound and highly intense experiences occurred. The first overarching category comprised the encounter with other ‘beings’ (94% of reports), encompassing super-ordinate themes including the entities’ role, appearance, demeanour, communication and interaction; while the second overarching category comprised experiences of emerging into other ‘worlds’ (100% of reports), encompassing super-ordinate themes of the scene, the contents and quality of the immersive spaces. Many further mid-level themes and subthemes also illuminate the rich content of the DMT experience.

Discussion: The present study provides a systematic and in-depth analysis of the nuanced content of the otherworldly encounter within the breakthrough DMT experience, as well as elaborating on the resonances both with previous DMT studies focusing on entity encounters and other types of extraordinary experiences entailing such encounters. These include the alien abduction, folkloric, shamanic and near-death experience. Putative neural mechanisms of these features of the DMT experience and its promise as a psychotherapeutic agent are discussed in light of such findings.

Maladaptive daydreaming is a proposed disorder characterized by excessive daydreaming that causes subjective distress and/or interferes with function. The daydreaming involves complex inner worlds, characters, and plots that are understood by the person as fantasy, and the daydreaming may occupy many hours per day. The disorder has good reliability and validity in studies using a structured interview and a self-report measure developed for it. To date, no information on the responses of maladaptive daydreamers to either recreational or prescription drugs has been available. The authors obtained survey data from 202 participants who completed the Maladaptive Daydreaming Scale-16. The results indicated that this population has tried many different recreational drugs and has been prescribed many different psychotropic medications. Most of the participants reported little to no effect of drugs or medications on daydreaming, although tentative recommendations can be made in favor of prescribing antidepressants and against the use of marijuana for individuals with maladaptive daydreaming.

Rationale and objectives The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin receptor agonist/5-HT 2c serotonin receptor antagonist. Results Adult PRS rats showed behavioral, cellular, and biochemical abnormalities that were consistent with an anxious/depressive phenotype. These included an increased immobility in the forced swim test, an anxiety-like behavior in the elevated plus maze, reduced hippocampal levels of phosphorylated cAMP-responsive element binding protein (p-CREB), reduced hippocampal levels of mGlu2/3 and mGlu5 metabotropic glutamate receptors, and reduced neurogenesis in the ventral hippocampus, the specific portion of the hippocampus that encodes memories related to stress and emotions. All of these changes were reversed by a 3-or 6-week treatment with agomelatine (40-50 mg/kg, i.p., once a day). Remarkably, agomelatine had no effect in age-matched control rats, thereby behaving as a "diseasedependent" drug. Conclusions These data indicate that agomelatine did not act on individual symptoms but corrected all aspects of the pathological epigenetic programming triggered by PRS. Our findings strongly support the antidepressant activity of agomelatine and suggest that the drug impacts mechanisms that lie at the core of anxious/depressive disorders.

Luke, D., Terhune, D & Friday, R. (2012). Psychedelic synaesthesia: Evidence for a serotonergic role in synaesthesia. Seeing and Perceiving, 25, 74.

The neurobiology of synaesthesia is receiving growing attention in the search for insights into consciousness, such as the binding problem. One way of decoding the neurocognitive mechanisms underlying this phenomenon is to investigate the induction of synaesthesia via neurochemical agents, as commonly occurs with psychedelic substances. How synaesthesia is affected by drugs can also help inform us of the neural mechanisms underlying this condition. To address these questions we surveyed a sample of recreational drug users regarding the prevalence, type and frequency of synaesthesia under the influence of psychedelics and other psychoactive substances. The results indicate that synaesthesia is frequently experienced following the consumption of serotonergic agonists such as LSD and psilocybin and that these same drugs appear to augment synaesthesia in congenital synaesthetes. These results implicate the serotonergic system in the experience of synaesthesia.

Bipolar duygudurum bozukluğunda eşik altı belirtilerin fark edilmemesinin bazı vakaların tanı ve tedavisini güçleştirdiği gözlenmektedir. Bu yelpazede yer alan hastaların işlevsellik düzeyinde önemli bozulmalar olduğu, hastanın hastalığı kabul sürecinin ve tedavi uyumunun bozulduğu düşünülmektedir. Bu yazıda bipolar yelpaze kavramı içinde değerlendirilen bir vakanın tanı ve tedavi süreci anlatılacaktır.
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It has been reported that the correct diagnosis and treatment are delayed when subsyndromal bipolar mood disorder symptoms are overlooked. Patients in this spectrum are also reported to have a dimished level of functioning, and these patients also fail to accept their diagnosis, and therefore there is a low level of treatment adherence. This case report focuses on the diagnosis and treatment of a patient in the bipolar spectrum.