Significant Psychedelic Experiences Evaluated for Mystical Characteristics Associated with Cannabis Use Reduction and Psychological Flexibility Improvement: A Naturalistic Cross-Sectional Retrospective Survey.

Treating cannabis use disorder remains a significant challenge in the field of addiction medicine. Some recent studies point to psychedelic-assisted psychotherapy as a potential treatment option for substance use disorders. The objective of this study was therefore to explore the impact of naturalistic psychedelic experiences on cannabis use and psychological flexibility. An online retrospective survey was carried out on 152 cannabis users who also reported a significant experience induced by psychedelics in the past. Following a psychedelic experience, there was a significant and sustained reduction of average CUDIT score (p < .001), frequency of cannabis use (p < .001), and acute duration of daily intoxication (p < .001). Cannabis use reduction during the first month post-experience was significantly associated with the intensity of the mystical experience (p = .01). Participants reported a concomitant increased lasting improvement of psychological flexibility following the experience (p < .001), which was correlated to the intensity of the mystical experience during the first month post-experience (p = .04). This study demonstrates that naturalistic psychedelic experiences may be followed by a decrease in cannabis use. Positive health outcomes appear potentially connected to the intensity of the mystical experience, as well as an improvement in psychological flexibility.

Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review.

Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and meta-analysis was to evaluate safety data in human subjects. We carried out a search on MEDLINE, Embase and PsycINFO databases between 2000 and 2022. Standardized mean differences between different dose ranges and between acute and subacute phases were calculated for cardiovascular data after psychedelic administration. Risk differences were calculated for serious adverse events and common side effects. Thirty studies were included in this meta-analysis. There were only nine serious adverse events for over 1000 administrations of psychedelic substances (one during the acute phase and 8 during the post-acute phase). There were no suicide attempts during the acute phase and 3 participants engaged in self-harm during the post-acute phase. There was an increased risk for elevated heart rate, systolic and diastolic blood pressure for all dose range categories, as well as an increased risk of nausea during the acute phase. Other common side effects included headaches, anxiety, and decreased concentration or appetite. This meta-analysis demonstrates that psychedelics are well-tolerated, with a low risk of emerging serious adverse events in a controlled setting with appropriate inclusion criteria.

Impact of a Naturalistic Psychedelic Experience on Smoking: A Retrospective Survey.

Tobacco use disorder is a major public health concern. The aim of this study was to investigate the impact of a psychedelic experience in a natural context on tobacco use. A retrospective online survey was conducted on 173 individuals who reported having had a psychedelic experience while being smokers. Demographic information was collected, and characteristics of the psychedelic experience, tobacco addiction and psychological flexibility were assessed. Mean number of cigarettes smoked per day, and proportion of individuals with high tobacco dependency significantly decreased between the three time points (p < .001). Participants who reduced or quit smoking had more intense mystical experiences during the psychedelic session (p = .01) and lower psychological flexibility before the psychedelic experience (p = .018). The increase in psychological flexibility post psychedelic session, and the personal motives for the psychedelic experience were significant positive predictors of smoking reduction or cessation (p < .001). Our results confirmed that a psychedelic experience in smoker individuals can be associated with smoking and tobacco dependency reduction and that the personal motives for the psychedelic session, the intensity of the mystical experience, and the increase of psychological flexibility following the psychedelic experience, are associated with smoking cessation or reduction.

Recent advances in drug design of epidermal growth factor receptor inhibitors.

The tyrosine kinase epidermal growth factor receptor (EGFR) has emerged in recent years as a key and validated target of targeted therapies for solid tumors. It plays a central role in oncology since it is involved in many steps of tumor progression such as proliferation, angiogenesis, invasiveness, decreased apoptosis, and loss of differentiation. Recent advances in targeted therapies have demonstrated that tyrosine kinase inhibitors (TKIs), have provided a marked benefit to subsets of patients whose tumors harbor specific genetic abnormalities. However, resistance phenomenon appears rapidly and patients with EGFR mutations acquire resistance to TKI inhibitors decreasing therefore the median time to disease progression to few months. Several strategies were envisioned to overcome this resistance, such as dual-target inhibitors, multitarget and combined therapy. This review summarizes recent advances in TKIs development with special focus on rational strategies for the design of potent EGFR inhibitors including molecular modeling studies based on crystallographic data. Such advances open the way for new research possibilities in modern medicinal chemistry combined to structure-based drug design.