Journal of Psychopharmacology最新文献

Background: Due to the unsatisfactory therapeutic effects of current antidepressants, research has been launched into alternative treatment approaches, such as the administration of psychedelics. Psilocybin, a classic hallucinogen, has been shown to exert considerable positive influence on depression symptoms through its serotonergic and glutamatergic effects. This systematic review and meta-analysis aimed to evaluate the effectiveness of psilocybin in treating depression.

Methods: A comprehensive search of Medline (via PubMed) and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the therapeutic impact of psilocybin on depression. A mixed-effects multi-level model was used to estimate the overall effect size. Effectiveness over time was also investigated as a secondary analysis.

Results: The results of the primary analysis revealed a large and clinically observable reduction (SMC: -1.24, 95%CI: -1.83 to -0.65, I²_level2 = 11.39%, I²_level3 = 77.67%) of depressive symptomatology in patients receiving psilocybin in addition to supportive therapy compared to baseline measurements. The decrease was also marked when compared to placebo (p-value = 0.032). The results remained significant even when a secondary analysis assessed the effect in various time intervals since the administration of psilocybin.

Conclusion: This systematic review and meta-analysis substantiate the claim that psilocybin is superior in treating depression compared to established psychotherapy alone used for treating depression. This finding warrants further studies with larger sample sizes and across a longer timeframe.

Background/aims: While most psychedelic substances are considered to carry a relatively low risk of acute or long-term harm, co-use with other psychoactive substances may increase health and social harm. Using a large international survey of adults who use psychedelics, we sought to comprehensively characterize psychedelic co-use.

Methods: We used data from the 2023 Global Psychedelic Survey, a web-based survey of adults ⩾21 with lifetime use of psychedelics. We explored patterns of co-use (prevalence, secondary substances used, timing, and motives of co-use) and examined sociodemographic and psychedelic use-related characteristics associated with co-use overall and by specific psychedelics.

Results: In total, 5370 respondents were included in this analysis, of whom 3228 (56.3%) reported typically co-using at least one of the 11 psychedelic substances of interest, with co-use lowest for ayahuasca (14.8%) and highest for nitrous oxide (54.5%). Cannabis and alcohol were the most common secondary substances. Depressants were the only secondary substance class that increased in use following psychedelic experiences. Greater experience with psychedelics was significantly associated with co-use, as was using for recreational purposes or to reduce/substitute the use of other substances. Personal exploration and therapeutic purposes for psychedelic use were negatively associated with co-use.

Conclusions: In this detailed analysis of psychedelic co-use, we observed high rates of co-use with certain psychedelics, specifically when used recreationally. Our findings highlight psychedelic-specific consumers for whom harm reduction messaging around co-use practices may be best tailored. Further research is justified to assess whether specific patterns of co-use might reduce or increase potential harms.

Posttraumatic stress disorder (PTSD) is a condition that can develop after a traumatic event, causing distressing symptoms, including intrusive re-experiencing symptoms, alterations in mood and cognition, and changes in arousal and reactivity. Few treatment options exist for patients who find conventional psychotherapy and pharmacotherapy to be inaccessible, ineffective, or intolerable. We explore psilocybin as a potential treatment option for PTSD by examining the neurobiology of PTSD as well as psilocybin's mechanism of action. Based on both pharmacodynamic and psychoanalytic principles, psilocybin may be an underexplored treatment option for patients with PTSD, though further research is required.

Background: Psychedelic substances reliably induce marked altered states of consciousness (ASC), which may be important for lasting effects and clinical outcomes of psychedelic intervention. Several instruments are available to measure the acute psychedelic experience, of which the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is commonly used. The questionnaire can be scored and analyzed as having five dimensions or 11 subscales, but the two have not been evaluated with comparable factor analysis methods.

Methods: The Danish translation of the 5D-ASC was completed by one sample of healthy volunteers receiving psilocybin in a laboratory setting (N = 47) and one sample of recreative users5D-ASC of psychedelics (N = 550), who reported retrospectively through an online survey based on their most recent experience with psilocybin. We calculated internal consistency measures of Cronbach's alpha and McDonald's omega, conducted a confirmatory factor analysis of the previously suggested factor structures, and tested for possible associations between the 5D-ASC total scores and dose, setting, and intention. For the 11 subscales, we reported omega-sem (composite reliability) using the parameters of the fitted confirmatory factor analyses model.

Results: Confirmatory factor analysis showed that the 11 subscales had a good fit to data and showed a better fit compared to the originally proposed five-dimensional solution and good internal consistencies. We further found that the 5D-ASC total scores correlated positively with the dose in the recreative sample. We found no correlations between 5D-ASC total scores and intention or setting.

Discussion: We find the Danish 5D-ASC to be a valid tool for measuring ASC among Danish-speaking individuals.

Background: Clinical trials demonstrate that psychedelic-assisted therapy can improve mental health outcomes; however, few studies have recruited sexually diverse samples or reported information on sexual identity.

Aims: The purpose of this analysis was to examine the relationship between hallucinogen use and mental health outcomes with respect to sexual identity.

Methods: We conducted a cross-sectional analysis using data from the 2021 National Survey on Drug Use and Health to examine the relationship between hallucinogen use and psychological distress.

Results: In a sample representative of 253,824,662 U.S. adults, the majority was heterosexual (92%), aged 50-64 (25%), women (51%), non-Hispanic White (62%), college educated (31%), and had an annual household income of $75,000 or higher (39%). The majority reported no lifetime hallucinogen use (82%) and no past month severe psychological distress (93%). Sexual identity modified the relationship between hallucinogen use and psychological distress. After stratifying by sexual identity and adjusting for covariates, hallucinogen use was associated with reduced odds of psychological distress in the heterosexual population (OR = 0.76, 95% CI: 0.59, 0.96) but the relationship was not significant in the sexual minority population.

Conclusion: We found that in a nationally representative sample, psychedelic use was associated with reduced odds of psychological distress in heterosexual individuals only. Future research should investigate why hallucinogen use was not protective in sexual minority groups given their disproportionate burden of poor mental health outcomes.

Background: Harmine is a component of the hallucinogenic brew, Ayahuasca, which also contains the psychoactive compound, N, N-dimethyltryptamine. Whether pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the doses at which these might occur, and the dose-response relationship to side effects and safety in humans are unknown.

Methods: We conducted a Phase 1, open-label single ascending dose trial in healthy adults with normal body mass index and no prior psychiatric illness. The primary goal was to determine the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A secondary goal was to ascertain whether any oral dose has psychoactive effects.

Results: Thirty-four adult participants, aged 18-55 years, were screened for study eligibility. Twenty-five participants met eligibility criteria and were randomized to a single dose of 100, 200, 300, or 500 mg of harmine HCl, respectively, using a continuous reassessment method. The most common adverse events (AEs) observed were gastrointestinal and/or neurological, dose-related, and of mild to moderate severity. The MTD was determined to be between 100 and 200 mg and is weight-based, with 90% of those participants receiving >2.7 mg/kg experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were identified.

Conclusions: Harmine HCl can be orally administered to healthy participants in doses <2.7 mg/kg with minimal or no AEs. Doses >2.7 mg/kg are associated with vomiting, drowsiness, and limited psychoactivity. This study is the first to systematically characterize the psychoactive effects of pharmaceutical quality harmine in healthy participants.

Background: Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT.

Aims: This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients, it also investigated the relationship between antidepressant effects and six measures of acute drug effects.

Methods: We compared data on acute psychedelic drug effects between 28 PAT patients with data from 28 healthy participants who participated in a randomized, double-blind crossover trial. All participants received varying doses of psilocybin and LSD. Subjective effects were assessed on an hourly basis during the acute drug effects, and the Mystical Experience Questionnaire (MEQ) was completed retrospectively. For patients, depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).

Results: Ratings of overall drug effect and mystical experience were similar across groups. Compared with healthy controls, patients reported lower ratings of ego dissolution. Patients showed a significant decrease in MADRS scores, and the greatest predictor of antidepressant outcome was relaxation during the PAT session. We did not observe a relationship between mystical-type experiences and antidepressant effects. Most patients experienced mild adverse effects which resolved within 48 h.

Conclusion: PAT reduced depressive symptoms in this heterogeneous patient group. Patients may experience more challenging psychedelic effects and reduced ego dissolution. Hourly assessment of drug effects may predict clinical outcomes better than retrospectively assessed mystical experiences, and the impact of relaxation during PAT should be investigated further.

Background: Non-ordinary states of consciousness induced by psychedelics can be accompanied by so-called "peak experiences," characterized at the emotional level by their intensity and positive valence. These experiences are strong predictors of positive outcomes following psychedelic-assisted therapy, and it is therefore important to better understand their biology. Despite growing evidence that the autonomic nervous system (ANS) plays an important role in mediating emotional experiences, its involvement in the psychedelic experience is poorly understood. The aim of this study was to investigate to what extent changes in the relative influence of the sympathetic (SNS) and parasympathetic nervous systems (PNS) over cardiac activity may reflect the subjective experience induced by the short-acting psychedelic N,N-Dimethyltryptamine (DMT).

Methods: We derived measures of SNS and PNS activity from the electrocardiograms of 17 participants (11 males, mean age = 33.8 years, SD = 8.3) while they received either DMT or placebo.

Results: Results show that the joint influence of SNS and PNS ("sympathovagal coactivation") over cardiac activity was positively related to participants' ratings of "Spiritual Experience" and "Insightfulness" during the DMT experience, while also being related to improved well-being scores 2 weeks after the session. In addition, we found that the state of balance between the two ANS branches ("sympathovagal balance") before DMT injection predicted scores of "Insightfulness" during the DMT experience, as well as subsequent sympathovagal coactivation.

Conclusion: These findings demonstrate the involvement of the ANS in psychedelic-induced peak experiences and may pave the way to the development of biofeedback-based tools to enhance psychedelic therapy.