Journal of Psychopharmacology最新文献

Background: Cannabidiol (CBD) impacts brain regions implicated in anxiety reactivity and stress reactivity (e.g., amygdala, anterior cingulate cortex (ACC), anterior insula (AI)); however, placebo-controlled studies are mixed regarding CBD's anxiolytic effects. We previously reported that CBD expectancy alone can alter subjective, physiological, and endocrine markers of stress/anxiety; however, it is unclear whether these findings reflect altered brain reactivity. This study evaluated whether CBD expectancy independently alters amygdala resting-state functional connectivity (rsFC) with the ACC and AI following acute stress.

Method: Thirty-eight (20 females) healthy adults were randomly assigned to receive accurate or inaccurate information regarding the CBD content of a CBD-free oil administered during a single experimental session. Following a baseline resting state MRI scan, participants administered their assigned oil sublingually, engaged in a stress task (serial subtraction with negative feedback) inside the scanner, and underwent another resting state MRI scan. Amygdala rsFC with the ACC and AI was measured during each scan, and the subjective state was assessed at six time points. Outcomes were analyzed using ANCOVA.

Results: CBD expectancy (vs CBD-free expectancy) was associated with significantly weaker rsFC between the left amygdala and right ACC (p = 0.042), but did not systematically alter amygdala-AI rsFC (p-values > 0.05). We also replicated our previously reported CBD expectancy effects on subjective stress/anxiety in the scanner context.

Conclusion: CBD placebo effects may be sufficient to alter neural responses relevant to its purported anxiolytic and stress-relieving properties. Future work is needed to replicate these results and determine whether CBD expectancy and pharmacology interact to alter neural anxiety reactivity and stress reactivity.

Background: Mechanisms underlying psychostimulant euphoria remain poorly understood. In adult rats, positive emotional states are associated with alterations in 50-kHz ultrasonic vocalizations (USVs): specifically, "trill" calls are promoted over "flat" calls. Here, we investigated the effects of acute and repeated cocaine administration, and-based on previous findings with amphetamine-their possible dependence on beta-adrenergic receptors.

Methods: Adult male Long-Evans rats received intraperitoneal drug or saline injections before daily USV recording. Fourteen 50-kHz call subtypes were analyzed. In Experiments 1 and 2, cocaine (1-10 mg/kg) and propranolol (10 mg/kg) were tested alone. In Experiment 3, propranolol/cocaine interactions were sought within a conditioned place preference (CPP) procedure. Experiment 4 investigated acute and chronic cocaine effects (Phase 1), and propranolol/cocaine interactions either in an open field (Phase 2) or within a CPP procedure (Phase 3).

Results: In drug-naïve animals, cocaine increased the 50-kHz call rate, with sensitization developing rapidly. After more extended exposure, cocaine now also increased the relative prevalence of trill versus flat calls; effects on other subtypes were also revealed. The beta-blocker propranolol prevented neither cocaine CPP nor cocaine effects on USV emission or locomotion but exerted significant USV-related effects when given alone. CPP magnitude and USV-related measures were uncorrelated.

Conclusions: With long-term intraperitoneal administration, cocaine can alter the relative prevalence of several 50-kHz call subtypes; its ability to promote trill versus flat calls, in particular, is consistent with a positive affect interpretation. Cocaine's behavioral effects (i.e., USV-related, locomotor, CPP) appear independent of beta-adrenergic receptor activity.

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.

Background: The metabotropic glutamate type 5 (mGlu5) receptor has emerged as a potential target for the treatment of psychosis that is suggested to have greater efficacy than antipsychotic medications that are currently utilized.

Aims: This study sought to elucidate mechanisms of therapeutic action associated with the modulation of the mGlu5 receptor in a disordered system marked by dopamine dysfunction. We further explored epigenetic mechanisms contributing to heritable transmission of a psychosis-like phenotype in a novel heritable model of drug abuse vulnerability in psychosis.

Methods: F1 generation male and female Sprague-Dawley rats that were the offspring of two neonatal quinpirole-treated (QQ) or two saline-treated (SS) animals were tested on nicotine-conditioned place preference (CPP). Regulators of G protein signaling 9 (RGS9) and β-arrestin 2 (βA2), which mediate dopamine (DA) D₂ signaling, were measured in the nucleus accumbens shell, prelimbic and infralimbic cortices. Reduced Representation Bisulfite Sequencing (RRBS) was used to analyze the cytosine methylation in these brain regions.

Results: Pretreatment with the mGlu5-positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) 20 min prior to conditioning trials blocked enhanced nicotine CPP and mitigated aberrant G protein-dependent and -independent signaling in QQ animals. RRBS analysis revealed region-specific changes in several pathways, including nicotine addiction, dopamine synapses, and neural connectivity.

Conclusions: These results reveal an important region-specific mechanism of action for CDPPB in a system marked by enhanced DAD₂ receptor signaling. Results additionally reveal DNA methylation as an epigenetic mechanism of heritability, further validating the current model as a useful tool for the study of psychosis and comorbid nicotine use.

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.