Posttraumatic stress disorder (PTSD) is a serious and chronic mental health condition with limited effective treatment options. 3,4-methylenedioxymethamphethamine (MDMA)-assisted psychotherapy (MDMA-AT) has shown promise in phase 2 and phase 3 clinical trials, with many research participants reporting significant reductions in PTSD symptoms. However, the Federal Drug Administration (FDA) recently voted against recommending MDMA-AT, citing concerns about its risk-benefit profile. This systematic review aimed to assess current evidence from randomized control trials (RCTs) on the safety and efficacy of MDMA-AT for adults with PTSD to determine if it warrants consideration for approval. Two articles identified were excluded from our analysis due to their recent retraction from publication. In total, seven RCTs were identified, including 280 adult participants with PTSD (160 received MDMA; 120 received placebo). Data were independently reviewed, focusing on PTSD symptom reduction and safety. Of the six studies included in the efficacy analysis, five (83.3%) found significantly improved PTSD symptoms in the MDMA groups compared to placebo groups. In addition, 41.7% to 85.7% of participants receiving MDMA-AT no longer met PTSD criteria post-treatment, compared to 25.0% to 33.3% reported for placebo groups. In addition, the treatment appeared well-tolerated. These findings support the potential of MDMA-AT as a viable treatment option for the symptoms of PTSD, though additional research with strict ethical oversight should inform FDA approval.

Amid an evolving psychedelic drug policy landscape and limitations of existing substance use disorder (SUD) treatments, a novel addiction recovery paradigm has emerged involving augmentation of 12-Step program engagement with therapeutic psychedelic use. A preliminary qualitative analysis was initiated to describe this movement by examining real-world experiences of participants in remission from alcohol, opioid, and stimulant use disorders. Between November 2022 and February 2023, data collection was piloted with nine individuals reporting ayahuasca, ibogaine, psilocybin, and/or peyote use in combination with 12-Step engagement. Participants were intentionally recruited through a community partner to explore this emerging phenomenon; findings are not intended to generalize to broader 12-Step communities. Motivations included challenges with sobriety, psychological distress during abstinence, dissatisfaction with existing SUD treatments, and the relative accessibility of this community-based approach compared to clinical care. Participants highlighted reduced SUD-related cravings, psychospiritual mechanisms of behavior change, and synergistic effects of psychedelics with Steps 2, 4, and 11. Tensions with abstinence-oriented philosophies were acknowledged, and risks related to unsupervised psychedelic use were central to participants' narratives; however, participants ultimately found that psychedelics enhanced their recovery by deepening actionable Step-work and improving psychosocial well-being. Pilot findings underscore a need for further research into this low-cost, accessible approach.

Psychedelic-assisted interventions are emerging as potential treatments for substance use disorders, including alcohol use disorder (AUD). While recent randomized controlled trials suggest efficacy for certain psychedelics and related compounds in treating AUD, the impact of naturalistic psychedelic use on problematic alcohol consumption remains underexplored. This study examines associations between psychedelic use and AUD in a nationally representative sample ( = 139,524). Logistic regression was used to examine the association between AUD and past-year use of LSD, MDMA, and ketamine, controlling for demographics and comorbid substance use. Past-year LSD use was significantly associated with lower odds of AUD (adjusted odds ratio [aOR] = 0.70,  = .006). However, use of MDMA (aOR = 1.17,  = .229) and ketamine (aOR = 1.28,  = .235) was not associated with AUD. In a quasi-Poisson regression analysis, past-year LSD use was found to be associated with 15.7% fewer AUD symptoms (IRR = 0.84, 95% CI: 0.72 - 0.98,  = .033), but neither past-year MDMA nor past-year ketamine use were significantly associated with AUD symptoms (MDMA: IRR = 0.97, 95% CI: 0.83 - 1.13,  = .731; ketamine: IRR = 1.21, 95% CI: 0.93 - 1.57,  = .139). Taken together, these findings indicate differential associations between specific psychedelics and AUD, with LSD use linked to a reduced risk of AUD. The results underscore the need for further research into the mechanisms by which LSD may influence alcohol use and AUD risk.

Attitudes about cannabis use (CU) are changing, as exemplified by laws in some states and the District of Columbia (DC) legalizing medicinal cannabis with or without recreational use. This study contrasts the effect of changes in DC and state laws with ongoing views of CU on the stigma of CU. Two hundred forty-six participants completed measures for this study. After reading a vignette about the current status of legalization across the United States, participants completed Likert-scale items that reflected their agreement with legalizing and stigmatizing medicinal and recreational use. Participants then complete the Stigma of Drug Users Scale (SDUS). Legal status of medicinal or recreational CU was not associated with indicators of stigma. Personal attitude about legality was significantly associated with stigma. Medicinal CU stigma was associated with the interaction of personal attitudes and actual state legality. Individual attitudes influence public stigma in states where medicinal CU is illegal, whereas in states where medicinal CU is legal, people's endorsement of legality decreased public stigma. Recreational CU stigma was also associated with this intersection. Although individual attitudes may not be overtly changed by their surroundings, the implicit effects and ramifications of such warrant our attention. There is also an opportunity to leverage environmental influences, for instance, strategically reconfiguring perceptions about institutional support, to optimize the effectiveness of interventions.

MDMA-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) shows promise, but attitudes and beliefs about this treatment, especially in symptomatic veterans, remain poorly understood. We sought to explore relevant attitudes in veterans receiving healthcare from Veterans Affairs as a step toward designing relevant surveys or psychoeducation materials for future work. We employed a story completion paradigm designed to sidestep aspects of self-report bias. Participants ( = 30) crafted narratives about an anonymous veteran with PTSD contemplating MDMA-AT. Coders rated transcripts, revealing recurring themes. At least one third of the sample mentioned shortcomings of available treatments, curiosity about its rationale, hope, and concerns about side effects, subjective effects, and the possibility of addictive potential. Despite widespread news coverage of the topics, allusions to therapist abuse, microdosing, and the role of sitters were relatively rare. At least 10% of the sample mentioned clear misunderstandings about the molecule, the treatment, or its implications. These data provide directions for the development of standard surveys of psychedelic-assisted treatments, which would help address these attitudes in larger samples. They can also inform psychoeducation materials that might help increase public awareness about this intervention, especially for veterans with symptoms.

Among adults who have used tianeptine, we aimed to determine demographic and substance-use patterns and gain insights into tianeptine doses, effects, and consumer conceptualizations. We also evaluated problematic use, quit attempts, and tianeptine-specific substance-use disorder (SUD). Between December 2023 and July 2024, an online survey was conducted. Participants were ≥18 years old and endorsed lifetime use of kratom, kava, tianeptine, and/or akuamma seed. Of the 369 respondents, 6.0% ( = 22) reported lifetime tianeptine use; they were 35.6 years old on average, White, and male (81.8%) and evinced diverse substance use. Mean age of tianeptine-use initiation age was 31.0. More within the tianeptine-use group believed they currently had any SUD (40.9% versus 20.2%,  = .0002), had ever been prescribed methadone/buprenorphine (27.3% versus 8.1%,  = .009), and were interested in recovery (72.7% versus 28.8%,  < .0001). Use motivations included euphoria, self-management of psychiatric symptoms, and drug substitution. Tianeptine-tolerance onset was considered rapid (59.1%), with one-third experiencing adverse effects. For past-year tianeptine SUD ( = 15), 13.3% of participants were mild, 53.3% were severe. Many tianeptine conceptualizations were unfavorable: "habit-forming" (68.2%), "addictive" (68.2%), "problematic" (59.1%); 86.3% believed overdose was possible. Tianeptine was used at low rates in this sample of adults who consumed gray-market supplements and included unfavorable perceptions.

Craving is a core characteristic in Cocaine Use Disorder (CUD) associated to relapse and treatment adherence. The assessment of craving is challenging due to the complexities arising from the various theoretical perspectives. Valid and reliable measures of craving are crucial in research and clinical settings considering the length to minimize the burden of patients. The existing craving assessment tools available in Italy are limited, with most instruments validated for populations other than CUD. This study aimed to validate the Italian adaptation of the 5-item Weiss Cocaine Craving Questionnaire (WCCS), a brief measure of cocaine craving. The sample included 385 CUD patients (359 men; mean age: 37.77 ± 8.46) undergoing multidisciplinary treatment. The Italian WCCS demonstrated a unidimensional factor structure and good internal consistency (Cronbach's alpha and McDonald's omega = 0.86). Nomological validity was assessed through significant associations with the Symptom Checklist-90-Revised (SCL-90-R), particularly with dimensions related to obsessivity-compulsivity, anxiety, and depression. Predictive validity was supported by receiver operating characteristics (ROC) analyses, with specific cutoff points enhancing the scale's utility in classifying cocaine use patterns and predicting cocaine relapses. These findings indicate that the Italian WCCS is a reliable and practical tool for clinical and research settings.

In recent years, the potential psychological benefits of psychedelic drugs have garnered increasing interest from academic and medical communities. We conducted a systematic review of literature examining the association between psychedelic drugs use and intimacy. The initial search yielded 5,902 studies, of which 19 met the inclusion criteria. Studies varied in methodology, including placebo-controlled experimental designs, quasi-experimental designs, and retrospective self-reports. Positive intimacy-related outcomes were reported in all nine laboratory setting studies, including relationship satisfaction, connectedness, emotional disclosure, empathy, and affiliation, as well as decreased social anxiety. Of the 10 studies that relied solely on retrospective self-report, six identified positive intimacy-related experiences including relationship quality, interconnection, empathy, and closeness. Four of these studies identified negative intimacy-related experiences, including disconnection, social anxiety, and relationship dissatisfaction and distrust. This systematic review demonstrates overwhelmingly positive effects of psychedelic drug use in research-controlled settings, but more research is needed to identify both the ideal settings for psychedelic drug use and the long-term impact of these drugs on intimacy.

5-Methoxy--dimethyltryptamine (5-MeO-DMT) is a psychedelic gaining interest as a potential mental health treatment. However, a poorly characterized phenomenon termed reactivation (similar to "flashbacks") is commonly reported with 5-MeO-DMT use and merits investigation. This study examined the prevalence, predictors, and emotional valence of reactivations among Spanish-speaking individuals. Specifically, we investigated whether gender, time planned ahead, intensity of acute effects, and the meaningfulness attributed to the experience predicted reactivation events. We also explored whether decreases in cognitive fusion were associated with reactivations, and whether these variables influenced the emotional valence of those experiences. A cross-sectional survey study was conducted with 90 respondents. Descriptive statistics and logistic regression analyses were employed to examine the aims. Sixty-nine percent of respondents reported reactivations, with 97% indicating the experience was positive or neutral. In the multivariable logistic regression model, longer time planned ahead and decreases in cognitive fusion significantly predicted reactivations. Challenging experiences were associated with a lower likelihood of reactivations being perceived as positive, while psychological insight was linked to a higher likelihood of positive perceptions. Reactivations among this sample appear to be common and predominately perceived as positive or neutral. Their association with cognitive fusion decreases suggests potential clinical relevance worth further investigation.

Approximately 18% of U.S. adults have a substance use disorder (SUD), yet SUD treatment utilization rates remain low. Substance use problem recognition, or one's awareness that their substance use is harmful, is a key precursor to seeking SUD treatment. Despite low treatment utilization prevalence, research on factors that promote substance use problem recognition among those with SUD is limited. Using 2022 National Survey on Drug Use and Health (NSDUH) data and drawing on Andersen's health service utilization model, we examined associations of predisposing, enabling, and need characteristics with substance use problem recognition among adults with one or more SUDs with a focus on the relationships between SUD type(s) and problem recognition. The statistical approach utilized was generalized linear models for a Poisson distribution with a log link function. Compared to having alcohol use disorder-only, having multiple SUDs was associated with a higher likelihood of problem recognition, whereas opioid use disorder-only was significantly associated with a lower likelihood of problem recognition. Findings speak to the need for further efforts to aid in SUD problem recognition.

Since its resurgence, psychedelic research has garnered considerable attention, especially in mental health. Preliminary findings have indicated positive results regarding psychedelic-assisted psychotherapy. Despite promising findings, various researchers have voiced concerns regarding psychedelic research and its potential for volunteer bias. Participants willing to participate in clinical trials, for example, might differ dramatically from the general population. The current study attempts to identify the potential volunteer bias that might contribute to current results. Participants recruited on MTurk ( = 702) provided demographic information as well as self-reported psychedelic use. We used binary logistic regressions to assess whether demographic and reported psychedelic use variables predicted willingness to participate in six hypothetical psychedelic studies. Results indicated that psychedelic use increased willingness to participate in a single unpaid survey, multiple unpaid surveys presented longitudinally, as well as an unpaid administration study. No demographic variables predicted volunteering consistently. Differences between paid and unpaid participation suggested that compensation might help reach broader samples. Given the implications related to volunteer bias and impeded generalizability, these findings indicate a need for further research to fully address the concern of volunteer bias in psychedelic research. Reaching those with less psychedelic experience will likely be imperative to investigations of clinical implications.

The U.S. Drug Enforcement Administration (DEA) proposed a rule in which they intend to place the psychedelic phenethylamines 2,5-dimethoxy-4-chloroamphetamine (DOC) and 2,5-dimethoxy-4-iodoamphetamine (DOI) into Schedule I of the Controlled Substances Act. We investigated the epidemiology of use and availability of these substances. We investigated national trends in seizures of these compounds (which indicate availability) using DEA National Forensic Laboratory Information System (NFLIS) and High Intensity Drug Trafficking Areas (HIDTA) data. We also examined the prevalence of self-reported use on the National Survey of Drug Use and Health (NSDUH), a nationally representative sample of noninstitutionalized individuals aged ≥12 in the United States. The scientific literature was also systematically searched for reports of poisonings linked to use. Between 2005 and 2024, NFLIS received 795 submissions of drugs testing positive for DOC, with a peak of 152 in 2012. There was then a decrease through 2024, with only two submissions containing DOC in 2023-2024. Forty submissions contained DOI, with no submissions testing positive in 2019-2024. Three DOC seizures were recorded by HIDTA in 2017-2021, with none in 2022-2024. HIDTA had no recorded seizures of DOI. Between 2005 and 2023, there were 37 and 10 type-in mentions of lifetime DOC and DOI use, respectively, in NSDUH responses, suggesting a lifetime prevalence of < 0.01% among the noninstitutionalized U.S. population. We located three reports of poisonings linked to DOC use (in 2008-2024) and none linked to DOI use. Availability, recreational use, and poisoning related to the use of DOC and especially DOI appear to be rare.

Opioid use disrupts the hypothalamic-pituitary-adrenal (HPA) axis, altering stress responses depending on the stage of use. A higher cortisol/DHEA-S ratio may indicate relapse risk in substance use disorders. This study aimed to explore differences in serum cortisol/DHEA-S ratio and its association with proximal and perceived stress, social support, and coping strategies in opioid-dependent youth. In this study, we assessed 51 males aged 15-24 with opioid (heroin) use disorder from an Indian treatment center, categorized into three groups: recently admitted patients with opioid use, buprenorphine-maintained patients, and healthy controls ( = 17 each). Serum cortisol and DHEA-S levels were analyzed using ELISA. We found significant differences in cortisol ( < .001), DHEA-S ( < .001), and cortisol/DHEA-S ratio ( < .001) across groups. Recently admitted patients with opioid use had elevated cortisol/DHEA-S ratios (0.37), whereas buprenorphine maintenance with active coping strategies showed reduced ratios (0.22), indicating potential normalization of HPA axis function. Cortisol levels correlated positively with past-year stress in recent users, whereas the cortisol/DHEA-S ratio correlated negatively with social support. These findings suggest that buprenorphine maintenance, combined with effective coping and social support, may help normalize HPA axis imbalance, potentially reducing relapse risk in opioid-dependent youth. Further research is needed to confirm these findings and their implications for treatment strategies.

Psychedelic substances have gained attention for their therapeutic potential, yet they remain illegal in the UK. This study aimed to explore whether public attitudes toward UK drug policy predicted attitudes toward psychedelics, in terms of their legal status, the effects of psychedelics on individuals and society, the risks associated with psychedelic use, and personal openness toward psychedelic experiences and their potential positive effects. A cross-sectional survey was conducted with 250 participants aged 18-86 ( = 38.1,  = 15.8), using the APQ and sociodemographic measures. Multiple regression analyses revealed that viewing drug use as a health issue, rather than a criminal issue, was a significant predictor of support for psychedelic legalization and lower perceived risk. Additionally, gender, religious affiliation, political leaning, and prior drug use significantly influenced attitudes toward psychedelics. Women and religious individuals tended to view psychedelics as more harmful, while left-leaning and non-religious participants were more supportive of their therapeutic use. Participants with prior drug use experience were more open to psychedelics. These findings suggest that public attitudes may be influenced by broader drug policy perceptions and that shifts in policy framing toward health-based approaches could foster greater support for psychedelic reform. Further research should explore these associations longitudinally.

Polysubstance use is widespread among individuals who use drugs in the U.S. and can result in serious consequences. This study aims to understand frequent polysubstance use patterns among U.S. adults and compare these patterns between individuals with and without mental health (MH) conditions. Using data from the National Survey on Drug Use and Health for 2019-2022, we identified individuals who used one of ten substances in the past year. We then applied association analysis to extract co-use patterns of substances and estimate the strength of these associations. More than 42% of individuals reported using more than one substance in the past year. The top 10 polysubstance use patterns were largely consistent between individuals with and without MH conditions, although the prevalence and association of these patterns were higher among the MH group. In both groups, the most frequently co-used substances were marijuana and prescription opioids. Among the five illicit substances examined, heroin showed the highest conditional probability of co-use with cocaine or methamphetamine. This study demonstrated that there are similarities and differences in complex polysubstance use patterns between individuals with and without MH conditions. These findings can inform the development of targeted interventions tailored to particular substances and at-risk populations.

Interest in and use of hallucinogens appears to be growing in the United States, yet less is known about the use of multiple hallucinogens. The aims of this study are to characterize subgroups of lifetime hallucinogen use and to identify sociodemographic correlates of these subgroups. Latent class models were fit using 2021-2022 National Survey on Drug Use and Health (NSDUH) data on a sub-sample of individuals who reported having ever used any hallucinogen ( = 17,977). A four-class model identified the following subgroup classes: (16%), (46%), (23%), and a fourth class (15%) labeled , with high probabilities of use of psilocybin, LCD, and ecstasy, in addition to moderate probabilities of use of other hallucinogens. In survey-weighted multinomial logistic regression analyses, compared to the class, the adjusted odds of being in the class increased with age-group level (AORs = 1.5-6.4, 95% CIs:1.3-8.7), and non-White participants had higher odds of being in the class (AORs = 1.7-3.2, 95% CIs:1.1-4.4). As policies regulating and clinical practice with hallucinogens continue to evolve, these patterns of lifetime hallucinogen use demonstrate the overlapping nature of hallucinogen experiences in the U.S. population, which has implications for expanding clinical trial inclusion criteria and establishing a baseline for future trends.

Young adults use cannabis and experience negative consequences at high rates. Cannabis use motives include coping, conformity, enhancement, expansion, and social. Savoring involves focusing attention on positive events to intensify positive emotions. Savoring might be differentially protective or risky when considering motives in relation to cannabis outcomes. We examined the interactions between cannabis motives and savoring on cannabis frequency and consequences. Young adults ( = 154) who used cannabis at least weekly in the past month completed self-report measures. The interaction between coping and savoring was associated with cannabis use frequency ( = -0.04,  = .001), such that coping motives were positively associated with cannabis use frequency at low levels of savoring ( = 0.80,  = .002), but negatively associated with cannabis use frequency at high levels of savoring ( = -0.80,  = .002). The interaction between coping and savoring was associated with cannabis-related consequences ( = 0.01,  < .001), such that coping motives were positively associated with cannabis-related consequences at low levels of savoring ( = 0.44,  < .001), but not at high levels of savoring ( = 0.10,  = .47). Savoring may protect against the effects of coping motives on cannabis use frequency and related consequences. While these findings are preliminary, future work should explore how a savoring intervention might improve cannabis outcomes via changes in coping motives.

As medical cannabis legalization expands in the United States, more parents and people of child-bearing age are becoming medical cannabis patients (MCP). This analysis uses the theory of role strain to explore how parents navigate being an MCP in Pennsylvania. Twenty four semi-structured qualitative interviews with parents from an ongoing registry study of MCP were analyzed using an a priori codebook and complemented by codes to capture emergent themes. Additionally, memowriting was utilized to refine the analysis and validate findings. Parents described their cannabis use as supportive of their parental role through the reduction of physical and psychological symptoms, improvements to mood, and increased patience with children. However, participants also reported that fear of legal consequences and stigma around their medical cannabis use put strain on their role as parents. The MCP role both supports and strains the parental role depending on context and situation. Results indicate a need for more research among parents who are MCP, especially along lines of identity and factors such as race, and ethnicity.

Psychedelic-assisted therapies and ketamine are two modalities gaining attention in psychiatry for treating conditions such as depression, PTSD, and substance use disorders. However, perceptions of these treatments vary globally. This study explores the familiarity, attitudes, and perceptions of Jordanian physicians and medical students toward psychedelic substances, addressing a gap in Middle Eastern research. A cross-sectional study conducted from July to August 2024 utilized a validated online survey among medical students and physicians in Jordan. The survey covered demographics, familiarity to psychedelics and ketamine, attitudes toward their medical use, and concerns about risks and legality. Statistical analyses, including multivariate regression and factor analysis, assessed the influence of demographics on participant perspectives. Of the 1,985 respondents, most had limited familiarity to psychedelics. LSD was the most recognized substance, while fewer participants identified psilocybin or MDMA. familiarity and attitudes varied significantly by age, gender, and prior familiarity, with professional status showing no impact. Three attitude clusters emerged: opposers ( = 1000), cautious ( = 677), and supporters ( = 308), each influenced by different demographics. This study reveals a notable familiarity gap and mixed attitudes toward psychedelic therapies among Jordanian healthcare professionals, highlighting the need for targeted education to enhance understanding of these treatments in Jordan's medical community.

This study aimed to assess the severity of drug dependence and identify factors associated with high dependence among gay, bisexual, and other men who have sex with men (gbMSM) in Japan. Data were collected from a nationwide community-based online survey conducted from November 2022 to January 2023. gbMSM with a history of drug use completed the Japanese version of the Drug Abuse Screening Test-20 (DAST-20). Multivariable logistic regression explored factors linked to high DAST-20 scores. Of 4,472 cisgender gbMSM, 19.1% (853/4472) reported lifetime drug use, and 3.3% (146/4472) reported use in the past 12 months. Among 142 participants with a recent history of drug use, the most reported drugs were alkyl nitrites (38.7%, 55/142), methamphetamine (25.4%, 36/142), and cannabis (17.6%, 25/142). A total of 26.8% (38/142) had DAST-20 scores of 6 or higher, indicating intermediate to severe dependence. High DAST-20 scores (≥6) were associated with recent methamphetamine use (aOR: 6.85; 95% CI: 2.01-23.29), using drugs to escape reality (aOR: 3.17; 95% CI: 1.06-9.50), and fostering intimacy with the person recommending the drug (aOR: 3.97; 95% CI: 1.36-11.62). Expanding screening opportunities and ensuring access to psychosocial care are essential in providing tailored support services to gbMSM with diverse health needs.

This study explored whether law enforcement/first responder-reported fentanyl overdose response actions (such as administration of the opioid overdose reversal agent naloxone) differed between overdoses in which xylazine was, versus was not, suspected to be co-involved. Data were drawn from the Pennsylvania State Police's Overdose Information Network (ODIN) for 11,478 suspected fentanyl-involved overdoses, 137 reportedly co-involving xylazine, recorded across Pennsylvania (January 2018-January 16, 2025), excluding Philadelphia. We used relative frequencies, Fisher's exact tests, and binomial logistic regression to compare first responders' overdose response actions in suspected fentanyl overdose cases in which xylazine was, versus was not, reportedly co-involved. Naloxone was administered at the scene of 46.0% of the overdoses reportedly involving fentanyl and xylazine, vs. 67.3% of the reported fentanyl-no-xylazine overdoses. Multivariable regression results (among the suspected fentanyl overdoses in ODIN, adjusting for age, sex, race/ethnicity, year, county rurality, and other drugs suspected to be involved) indicated that suspected xylazine co-involvement was associated with 60% lower odds of naloxone administration (adjusted odds ratio, 0.40; 95% confidence interval, 0.28-0.57). Observed differences in overdose response based on suspected xylazine co-involvement support the importance of equipping first responders with the tools and training to recognize/manage the distinct challenges of xylazine-fentanyl-involved overdose.