Science AI Journal
Psychology · Research topic

Open research questions in Psychedelics and Drug Studies

68 unresolved questions extracted from the limitations and future-work sections of 675 Psychedelics and Drug Studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Although no significant adverse events were reported, suggesting a potentially favorable safety profile in the short term, long-term efficacy and safety have not been established. Some additional studies suggest possible benefits of certain phytoestrogens (lignans and isoflavones), and betaine on selected cognitive domains, but findings are inconsistent and insufficient to support routine use [32, 33].

    Treatment of Cognitive Symptoms During Perimenopause: A Review · 2026 · DOI

  • Conclusions These findings suggest that HAR/DMT acutely modulates negative self-referential emotions and may, thus, offer a promising therapeutic approach, which should be further investigated in clinical populations.

    Combined DMT–harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers · 2026 · DOI

  • - Global psychedelic market: estimates vary widely (~$3B 2024 → ~$8B early 2030s, CAGR ~13%); Data Bridge, Precedence Research, Mordor Intelligence (2025/2026).

    Substanz-Tetralogie · 2026 · DOI

  • On the other hand, themes that emerged in antidepressant-related media were more critical, perhaps reflecting recent criticisms about the challenges of withdrawing from antidepressants, potential overprescribing, and contradictory evidence about the purported mechanisms of antidepressant medications [31]. While the pattern around positive tone was quite consistent, findings were mixed with measures of negative tone.

    Media hype regarding psychedelic treatments for depression and PTSD from 2017 to 2024 · 2026 · DOI

  • To broadly map available literature scoping reviews do not evaluate the quality or integrity of research studies. Further, given the scarcity of SW-related articles it was necessary to include grey literature. This review made a deliberate attempt to gather all literature meeting inclusion criteria regardless of publication status. It also presented SW roles at each level of practice as distinct despite that roles over- lap; this was an accepted assumption to provide specific rec- ommendations in various settings.

    "Riding the Wave"—Social Work Roles in Psychedelic Therapy Settings: A Scoping Review · 2026 · DOI

  • Several limitations warrant consideration. First, the modest sample size limited statistical power and precluded more complex models, including serial mediation analyses that could clarify causal cascades linking interoceptive awareness, phenomenology, and clinical outcomes. Second, altered states of consciousness were assessed only after the final float session, introducing temporal ambiguity regarding whether reported phenomenology reflects cumulative experience, peak effects, or session-specific states. This limits inferences about how phenomenological changes evolve across sessions or track symptom trajectories. Third, comparisons with psychedelic-induced altered states should be interpreted cautiously given heterogeneity in source studies, differences between healthy and clinical samples, data constraints within existing altered-states databases, and the use of visual, qualitative comparisons (i.e., radar plots) rather than direct statistical comparisons; future work with participant-level data could enable direct statistical testing. Notably, the finding that Spiritual Experience scores in Pool-REST Preferred exceeded those in psychedelics is limited by two factors: participants did not undergo both conditions, and the psilocybin data are stratified by dose. At higher doses (e.g., 400 µg/kg), Spiritual Experience scores surpassed those observed in Pool-REST Preferred sessions, suggesting the inversion may be partly attributable to collapsing across dose. Together, these limitations underscore the exploratory nature of the present findings and motivate larger, longitudinal, and mechanistically targeted studies.

    Aquahenosis: A non-pharmacological altered state of consciousness induced by Floatation-REST in individuals with anxiety and depression · 2026 · DOI

  • Several directions for future research emerge from these findings. Within-subject crossover designs directly comparing Floatation-REST and psychedelic interventions would provide a more rigorous test of whether non-pharmacological sensory perturbations can induce altered states comparable in magnitude and structure to pharmacologically induced experiences. Longitudinal assessment of phenomenology across float sessions would further clarify how altered states evolve over time, identify critical windows for therapeutic or experiential shifts, and enable formal testing of dose–response relationships. Larger-scale studies will be needed to test serial mediation models examining how changes in interoceptive awareness give rise to specific phenomenological states that, in turn, support affective or clinical improvements. Characterizing individual difference factors—such as absorption, openness to experience, or baseline interoceptive accuracy—may further enable personalized matching to consciousness-altering interventions and help predict whether ego dissolution is experienced as anxious or oceanic. The selective convergence between Floatation-REST and psychedelic phenomenology, particularly along the dimension of Oceanic Boundlessness, suggests opportunities to study Floatation-REST as a preparatory or adjunctive intervention for psychedelic-assisted therapy. Such approaches could reduce anxiety surrounding altered states, enhance receptivity to self- transcendent experiences, or potentially allow lower pharmacological doses while preserving therapeutic mechanisms. Future work should also examine whether educational and contemplative scaffolding around the float experience (particularly intention-setting before sessions and structured integration afterward) can modulate the valence of any ego-dissolution phenomenology that emerges and, in turn, the magnitude of downstream therapeutic effects. Such pre- and post-session framing is increasingly central to psychedelic-assisted therapy (Carhart-Harris et al., 2018; Watts & Luoma, 2020), and analogous evidence from contemplative training (Dahl et al., 2015) suggests that interpretive frameworks shape whether self-deconstructive states are experienced as expansive or threatening. From a broader neuroscience of consciousness perspective, Floatation-REST offers a safe, legal, and experimentally tractable model for investigating how controlled sensory environments reshape bodily self-models and conscious experience. Future work integrating neuroimaging, computational modeling, and economic analyses of scalability may help position Floatation- REST within a broader ecosystem of consciousness-altering interventions, clarifying when and how non-pharmacological approaches can complement or substitute pharmacological ones.

    Aquahenosis: A non-pharmacological altered state of consciousness induced by Floatation-REST in individuals with anxiety and depression · 2026 · DOI

  • 10088 Published online by Cambridge University Press A limitation of this study was that only two databases were searched, even though MEDLINE and PsychInfo are two of the main databases for medical and psychological research, accordingly.

    The effects of psychedelics on attention deficit and hyperactivity disorder - a systematic review · 2026 · DOI

  • Several limitations of the current evidence base must be acknowledged. First, the majority of psilocybin trials have been conducted with relatively homogeneous populations in Western clinical settings, limiting generalizability. Second, blinding remains a significant methodological challenge, as the perceptual effects of psychedelic compounds make true placebo conditions difficult to achieve (Norring & Spigarelli, 2024). Third, the contribution of the therapeutic component versus the pharmacological component remains inadequately disaggregated in most trial designs. Future research priorities include: (a) larger, adequately powered Phase 3 trials with active comparator conditions; (b) development of standardized adverse event reporting frameworks; (c) longitudinal studies tracking outcomes beyond 12 months; (d) investigation of personality-informed treatment matching to optimize therapeutic specificity; and (e) research conducted in Latin American and other non-Western settings where traditional use of these compounds has the longest history.

    Responsible Ceremonial Medicine: A Review of Current Evidence, Safety Protocols, and Ethical Considerations for Professional Practice · 2026 · DOI

  • The primary limitation is the open-label, single-arm design, which cannot control for nonspecific factors such as placebo effects. The small sample size (N=20) limits the generalizability and ability to draw conclusions about the incidence of rare adverse events. The study was conducted at a single, specialized academic center with highly trained therapists, which may not reflect real- world clinical settings. An additional limitation is that more than half of participants restarted or initiated adjunctive pharmacotherapy for MDD after week 3. Although improvements on primary outcomes were evident before these changes, the introduction of additional medications complicates the interpretation of long-term durability as psilocybin was not a stand-alone intervention across the entire follow-up. Finally, the sample size on MSSI nonresponders at week 3 was small (N=5), limiting the reliability of the exploratory comparisons with responders. Additionally, the open- label design raises the possibility that expectancy effects contributed to the large observed effect sizes. Participants who volunteer for a psilocybin trial may harbor strong positive expectations, and the subjective profundity of the psychedelic experience may amplify confirmation bias. In the broader antidepressant literature, nonspecific effects account for a substantial proportion of improvement in depression trials; there is no reason to assume that the contribution of such effects would be smaller in psychedelic-assisted therapy. Future controlled trials with an adequate comparator condition will be essential to disentangle specific pharmacologic effects from expectancy and other nonspecific factors. CONCLUSION Despite these limitations, this pilot study provides a strong preliminary signal that psilocybin-assisted therapy warrants further investigation as a treatment for chronic suicidal ideation. A single dose of psilocybin was associated with rapid, robust, and durable reductions in suicidal ideation and depression. Future studies should employ a suitable comparator group and include long- term follow-up to assess the full durability of treatment effects.

    Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation · 2026 · DOI

  • Participant characteristics may not reflect the broad and evolving range of perspectives in the psilocy- bin community. Participants did not discuss the role of demographic factors in informed consent pro- cesses, despite the importance of culturally respon- sive consent, particularly given the heightened risks faced by less resourced individuals [53]. While par- ticipants emphasized the general power imbalance Vol.: (0123456789) 21 Page 16 of 19 Neuroethics (2026) 19:21 between clients and providers, other intersecting power dynamics are also critical to attend to (such as those relating to inequalities), especially given the increased risk factors for exploitation inherent in psy- chedelic services, including heightened vulnerability induced by mind-altering substances and physical touch as a common aspect of treatment. While the results are highly novel, they raise addi- tional questions and hypotheses for future research to rigorously assess associations between elements of consent and clinical outcomes. Future studies could empirically assess client outcomes and perceptions following the implementation of the informed consent processes described here. Additionally, future work should focus on establishing standards and a deeper understanding of how to integrate cultural respon- siveness into informed consent processes and adapt consent processes to unique contexts and populations. Future implementation science research on how to best translate the informed consent ideals delineated in the current paper into various psychedelic care set- tings remains an essential future research direction. The current results speak to informed consent ideals, which have long faced challenges in practical imple- mentation [32]. For instance, participants noted that meaningful consent requires time for nuanced conver- sations which can “go on for hours and hours” [p12]. Such extended informed consent conversations may presently be most feasible in clinical trial settings, which generally have three preparatory sessions, or in legacy (underground) settings, where implemen- tation may be more flexible. Offering this depth can be difficult in settings constrained by lack of insur- ance coverage (e.g., state-regulated psilocybin ser- vices), resources, or strict session time limits. Upon FDA approval, increased affordability and insurance coverage may improve the feasibility of extended informed consent processes. In light of these realities, some participants suggested that empowering clients to face uncertainty—rather than aiming for complete ‘informed consent’—may be more attainable and eth- ically sound [42]. Participants also emphasized the need for train- ing in complex clinical and relational skills, which require time and sustained practice to develop. Ensur- ing such training is both accessible and affordable will be essential for real-world implementation. In one study of Oregon’s Psilocybin Services Workforce, the majority of participants reported that training expenses were a moderate-to-severe financial strain [18]. Overall, despite best efforts to ensure adequate and ethical informed consent across psychedelic care contexts, several barriers remain that we hope can be partially mitigated through the suggestions offered in this paper, including unrealistic treatment hopes/ expectations, power imbalances between clients and providers, difficulty understanding/asserting bounda- ries, and limited comprehension of long-term treat- ment impacts.

    Ethical Complexities and Best Practices in Informed Consent Processes for Psilocybin Services: A Qualitative Study · 2026 · DOI

  • Translational relevance Stress-based Social defeat, UCMS HPA axis, monoamines, plasticity Face validity, resilience Time, variability High…

    Neural signaling mechanisms in depression: bridging classical monoamine hypotheses, animal models, and emerging antidepressant strategies · 2026 · DOI

  • Further research delineating client and practitioner perspectives of naturalistic PAT services is warranted, and such work may shed light on the benefits and risks specific to naturalistic PAT as well as inform best practices for practitioners.

    Going Underground: Demographics, Services, and Best Practices Endorsed by Practitioners Providing Support for Naturalistic Psychedelic Use · 2024 · DOI

  • Although some people report naturalistic psychedelic use with so-called "underground" practitioners, little is known about PAT that occurs outside of controlled clinical settings or perspectives of these practitioners.

    Going Underground: Demographics, Services, and Best Practices Endorsed by Practitioners Providing Support for Naturalistic Psychedelic Use · 2024 · DOI

  • Little is known about the compound's historical use; this paper will explore and examine the known writings about the origins and original use of 5-MeO-DMT.

    Defining 5-MeO-DMT in Historical and Cultural Contexts · 2024 · DOI

  • Our findings suggest that RCT<apos;>s are warranted to test causal hypotheses concerning the effects of microdosing and the role of trait mindfulness in the effects of microdosing, while controlling for previous macrodose experience.

    Psychedelic Microdosing, Mindfulness, and Anxiety: A Cross-Sectional Mediation Study · 2022 · DOI

  • One open question related to PAT concerns the importance of the psilocybin experience of the guides (trained professionals present during acute effects).

    How Important Is a Guide Who Has Taken Psilocybin in Psilocybin-Assisted Therapy for Depression? · 2022 · DOI

  • Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.

    Psychedelics and Psychedelic-Assisted Psychotherapy · 2020 · DOI

  • The final section explores whether NDE and DMT experiences have a sufficient degree of phenomenological similarity to justify a causal role for DMT in the production of NDEs and concludes that such similarity is lacking.

    Does N,N-dimethyltryptamine (DMT) adequately explain near-death experiences? · 2012 · DOI

  • However, for reasons that continue to be poorly understood, clinical improvement following initiation of treatment with 5-HT reuptake inhibitors can take up to eight to 12 weeks, and most patients do not fully improve.

    Hallucinogens, Serotonin and Obsessive-Compulsive Disorder · 1998 · DOI

  • Abstract Research examining psychological outcomes following psychedelic use has grown substantially, yet the role of childhood trauma in shaping these responses remains insufficiently understood.

    Childhood trauma and psychological outcomes following psychedelic use: a scoping review · 2026 · DOI

  • In contrast, human studies have yielded mixed results: some reported that PSI increased PPI (Gouzoulis-Mayfrank, et al.

    Long- term administration of low doses of psilocybin causes epigenetic changes in the rat medial prefrontal cortex · 2026 · DOI

  • The Entropic Brain Theory proposes that states of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, but this prediction has not been tested across pharmacological and clinical perturbations within a common analytical pipeline.

    A Shared Entropic Axis Spans States of Consciousness Across Pharmacological and Clinical Conditions · 2026 · DOI

  • Prominent theories suggest that psychedelics have a lasting effect on hierarchical brain circuits, reducing top-down influence on information processing to facilitate an unbiased, bottom-up reassessment of the world, but direct and concrete evidence for such an effect is lacking.

    Psychedelics relax predictive processing in the post-acute period by remodeling cortico-cortical feedback circuits · 2026 · DOI

  • Despite encouraging Phase III trial results, the psychological mechanisms underpinning MDMA’s therapeutic effects remain insufficiently understood.

    Protocol for a qualitative mechanistic study of MDMA with a sample of psychoanalytic psychotherapists: A phenomenological investigation · 2026 · DOI

Most-cited papers in Psychedelics and Drug Studies

Most recent work

Find a gap in your own Psychedelics and Drug Studies sub-topic

This page shows what the Psychedelics and Drug Studies literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.

Open the Research Gap Finder →

Related topics in Psychology

LGBTQ Health, Identity, and Policy
750 open questions
Child and Adolescent Psychosocial and Emotional Development
645 open questions
Reading and Literacy Development
599 open questions
Posttraumatic Stress Disorder Research
543 open questions
Suicide and Self-Harm Studies
482 open questions
Child Abuse and Trauma
462 open questions
Attachment and Relationship Dynamics
453 open questions
Family and Disability Support Research
453 open questions
68 open questions have been extracted from the limitations and future-work passages of 675 Psychedelics and Drug Studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 120,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? A Tier 1–5 acceptance probability in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck prior-publication & salami-slicing risk across 8 sources.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.