2025-10-26

The Clinical Viability of Tryptamine-Based Pharmacotherapy for Major Depressive and Mood Disorders

depression, DMT, medication, psychiatry, research, risk, treatment

Estimated reading time at 200 wpm: 21 minutes

The field of mental health treatment is witnessing a surge of interest in psychedelic compounds, and Dimethyltryptamine (DMT) is at the forefront of this movement. However, for those following the headlines, it is essential to understand the current status: DMT-based medicines are not yet approved or commercially available.

Research into these powerful compounds, particularly the ultra-short-acting analogue 5-MeO-DMT, is still in the mid-stage of clinical testing (Phase 2).

Whether or not you agree our Fat Disclaimer applies

This article is in two parts. The first part is for non-academics. The academic version is at the end.

Despite being unapproved, the research is moving quickly. One leading candidate, BPL-003, has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA). This special status indicates that the FDA believes the treatment could offer a significant advantage over existing therapies for people with severe, Treatment-Resistant Depression (TRD).

The Ultra-Fast Advantage

The unique potential of DMT therapies lies in their ultra-short duration. Unlike traditional psychedelic therapies that require hours of clinical supervision, drugs based on 5-MeO-DMT are designed to work in an intervention window of just 15 to 30 minutes.

This rapid action offers immense practical benefits for healthcare systems. By minimising the time a patient needs to spend under clinical observation, the logistical complexity and operational costs of the treatment are drastically reduced, potentially making it much easier to deliver at scale.

Evidence of Potent Effects

While clinical trials for pure DMT compounds are ongoing, the most robust evidence for its powerful effect comes from a randomised controlled trial (RCT) involving Ayahuasca (a substance that contains DMT). This trial demonstrated exceptionally strong antidepressant results against a placebo.

Quantitatively, the effects observed were significantly larger than those typically associated with standard antidepressants. The magnitude of benefit, measured by an effect size (Cohen’s ), was 1.49 after just seven days. Furthermore, emerging data suggests this rapid improvement can be sustained for up to three months following a two-dose regimen. This indicates DMT is not meant to be a daily medication, but rather an intermittent therapy designed to offer prolonged relief from a single, brief intervention.

Safety and the Serotonin Risk

In early, small-scale trials, 5-MeO-DMT formulations have shown a favourable short-term safety profile. Adverse events are generally mild and temporary, mostly limited to nausea, headache, and anxiety, and they resolve spontaneously . Crucially, no serious adverse events (SAEs) have been reported in these early cohorts .

However, there is a critical safety warning: DMT is chemically similar to serotonin. Combining it with standard antidepressants, such as SSRIs or MAOIs, carries a high risk of causing a life-threatening condition called Serotonin Syndrome . Consequently, patients must undergo a mandatory and rigorous “washout” period, stopping their current medication before starting DMT therapy.

The Blinding Challenge

Finally, experts caution that the extraordinarily large effect sizes reported must be interpreted carefully. The psychoactive experience induced by DMT is so profound that it is virtually impossible to maintain blinding (where neither the patient nor the doctor knows if the patient received the active drug or a placebo).

When patients are unmasked and are highly hopeful (high expectancy) of a positive outcome—a common issue in psychedelic trials—the perceived benefits of the drug can be exaggerated. Experts estimate this expectation bias can inflate positive results by up to 0.56 standard deviations. Future large-scale trials must address this methodological challenge to provide definitive, regulator-approved evidence of the true drug-specific benefit.

Despite these hurdles, the rapid action, potent early efficacy, and logistical advantages of DMT-based therapies position them as a highly promising, and rapidly advancing, frontier in the treatment of severe mood disorders.

Pharmaceutical formulations of DMT and its analogues are currently in the mid-stage of clinical research (Phase 2) and have not yet completed all necessary trial phases for regulatory approval. Larger Phase 2 Randomised Controlled Trials are currently ongoing ¹, such as the one investigating BPL-003.² Therefore, these compounds are not commercially available as approved prescription treatments for depression or mood disorders. Research is rapidly progressing, however, with candidates like BPL-003 having received FDA Breakthrough Therapy Designation for Treatment-Resistant Depression.³

I. Executive Summary: Strategic Landscape, Key Data Insights, and Investment Thesis

The therapeutic potential of psychedelic compounds, specifically those derived from tryptamines, has garnered significant clinical and regulatory interest in the treatment of severe mood disorders. Current evidence indicates a substantial efficacy signal for these agents, complemented by logistical advantages that position them strategically for rapid development and scaling.

A. Status of DMT-Based Therapies in Mood Disorders

Contemporary clinical development has strategically focussed on the ultra-short-acting analogue, 5-methoxy-$N,N$-dimethyltryptamine (5-MeO-DMT, also known as Mebufotenin), rather than the longer-acting $N,N$-DMT. This focus is driven by the logistical and commercial superiority of an agent that offers rapid onset and significant efficacy within a short therapeutic window.⁵ The short 15–30 minute intervention window ⁵ fundamentally shifts the logistical and commercial proposition of psychedelic treatment. This ultra-short duration minimizes the required time commitment for clinical staff and patient monitoring, significantly lowering the necessary therapeutic infrastructure and operational costs per session compared to traditional long-acting psychedelics. This critical factor provides a clear path toward scalability and enhanced profitability in the delivery model.

This strategy has achieved significant regulatory validation. BPL-003 (a formulation of 5-MeO-DMT) has received U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation (BTD) for the treatment of Treatment-Resistant Depression (TRD).³ This designation confirms the FDA’s confidence in the clinical programme’s potential to deliver substantial improvement over existing treatments for patients with high, unmet medical need.³

B. Quantitative Efficacy Benchmarks

The most robust, published evidence for the efficacy of the DMT mechanism comes from placebo-controlled trials involving Ayahuasca (a plant mixture containing DMT and monoamine oxidase inhibitors or MAOIs). One established randomised controlled trial (RCT, NCT02914769) provides critical proof-of-mechanism data, demonstrating rapid and potent antidepressant effects against placebo in Major Depressive Disorder (MDD).⁶

The quantitative findings from this trial revealed exceptionally large effect sizes (Cohen’s $d$) when comparing the Ayahuasca group to placebo. Effect sizes were high immediately, with Cohen’s $d = 0.84$ observed at Day 1 and Day 2, which then amplified to a very large effect size of Cohen’s $d = 1.49$ at Day 7.⁶ Furthermore, emerging Phase 2 data for 5-MeO-DMT analogues suggest promising durability. Open-label data for BPL-003 indicates that rapid antidepressant effects are sustained for up to three months, with enhanced response achieved through a two-dose induction regimen.⁷ Other sponsored Phase 2 data for GH001 (5-MeO-DMT) reports high remission rates, with 57.5% of subjects achieving remission at Day 8.⁸

C. Critical Risks and Expert Caveats

While the effect sizes are highly encouraging, their interpretation must be approached with caution due to acknowledged methodological limitations inherent in psychedelic RCTs. The profound psychoactive nature of these compounds creates a significant risk of de-blinding (breaking the blind), meaning participants and often therapists can correctly guess whether the active drug or a placebo was administered.⁹ In general medical RCTs, this unmasked environment can exaggerate effect sizes by up to 0.56 standard deviations.⁹ Applying this potential inflation to the large Cohen’s $d = 1.49$ observed in the Ayahuasca trial indicates that final, methodologically controlled efficacy metrics may be lower.

A further critical risk involves patient safety protocols. DMT is structurally related to the neurotransmitter serotonin, and its use alongside other serotonergic drugs, such as Selective Serotonin Reuptake Inhibitors (SSRIs) or MAOIs, carries a serious, potentially life-threatening risk of Serotonin Syndrome.¹⁰ This necessitates extremely rigorous clinical exclusion criteria and mandatory washout periods for patients on concurrent antidepressants, influencing the entire clinical protocol design.

II. Pharmacological and Therapeutic Differentiation: The Tryptamine Class

Defining the specific pharmacological characteristics of $N,N$-DMT and 5-MeO-DMT is essential to understanding their mechanism of action and their specialised application in treating mood disorders.

A. Tryptamine Chemistry and Receptor Profile

$N,N$-DMT and its analogues are naturally occurring endogenous tryptamines, sharing structural similarity with the key mood regulator, serotonin.¹⁰ Both compounds exhibit high affinity for a range of monoamine receptors, primarily focussing on serotonergic (5HT) receptors, notably the 5HT2A receptor, which mediates the classic psychedelic experience, and the 5HT1A receptor.⁵ This dual agonism, particularly the activity at 5HT1A, is significant, as this receptor is often associated with acute anxiolytic and antidepressant effects. The involvement of 5HT1A agonism may be mechanistically linked to the hypothesised efficacy of 5-MeO-DMT that is independent of prolonged integrative therapy, facilitating a rapid psychological shift or “reset” and potentially reducing reliance on the protracted, subjectively challenging experience characteristic of some other classic psychedelics.⁵

In terms of metabolism, the compounds are rapidly processed. Suggested metabolic pathways for DMT include oxidation by peroxidases, leading to metabolites such as kynuramine derivatives, or the formation of 1,2,3,4-tetrahydro-beta-carboline (THBC).¹¹ Attention to these metabolic pathways is crucial for assessing long-term pharmacology and safety.

B. The Ultra-Fast Paradigm: Duration and Intensity

DMT and 5-MeO-DMT represent the ultra-fast, short-acting class of psychedelics. $N,N$-DMT, when administered (such as intravenously or inhaled), produces an extremely intense, yet transient, visual and auditory hallucinogenic experience.¹⁰ 5-MeO-DMT operates under an even shorter therapeutic window. The rationale driving its clinical development is that the potent, acute engagement of neuroplastic mechanisms results in a durable effect following an intense, brief intervention lasting only 15–30 minutes.⁵

The commercial viability of this rapid action hinges on specialised formulation and delivery. Due to the very short half-life of these compounds, achieving consistent bioavailability and rapid onset requires advanced systems, such as the intranasal formulation utilised by BPL-003.⁷ The success of these formulation efforts validates the engineering required to stabilise and standardise dosing for these fast-acting compounds, enabling the implementation of the “ultra-short” therapeutic model.

C. Exclusion of Irrelevant “DMT” Protocols

In compliance with the requirement for robust pharmacological evidence, this review strictly excludes non-pharmacological or unrelated medical uses of the acronym DMT. This includes Dance/Movement Therapy (DMT) trials, which address aging or depression through movement activities ¹², and Disease Modifying Therapies (DMTs) used for Multiple Sclerosis, such as fingolimod or natalizumab, which operate under entirely different pharmacological mechanisms.¹⁴

III. Quantitative Efficacy Review of Approved Trials and Advanced Data

A. Efficacy of Ayahuasca (DMT + MAOIs): The Primary RCT Evidence Base

The most definitive randomised, placebo-controlled data on the anti-depressant power of the DMT mechanism is derived from a trial (NCT02914769) involving Ayahuasca in MDD patients.⁶ This formulation includes DMT alongside Harmala alkaloids (MAO-inhibitors) which facilitate oral bioavailability.

The trial demonstrated significant antidepressant effects compared to placebo at all measured time points.⁶ A significant decrease in depression severity (measured by HAM-D and MADRS scales) was observed as early as 2 hours after intake.¹⁶ Critically, the between-group effect sizes (Cohen’s $d$) were exceptionally large, indicating a potent clinical impact: $d = 0.84$ at Day 1 and Day 2, increasing sharply to $d = 1.49$ at Day 7.⁶ This magnitude of effect size, which is substantially higher than typical conventional antidepressants, establishes a strong benchmark for the efficacy potential of tryptamines in the treatment of mood disorders. The antidepressant effect was maintained for 21 days following administration.¹⁶

The highly potent signal observed in the Ayahuasca RCT justifies the intense, rapid development of pure DMT and 5-MeO-DMT analogues. The $d=1.49$ finding demonstrates that the tryptamine mechanism, when pharmacologically optimised, achieves clinical outcomes far exceeding those typically seen with existing treatments, validating the accelerated investment in this class.

B. Emerging Phase 2 Results for 5-MeO-DMT (TRD)

The current clinical focus centres on proprietary formulations of 5-MeO-DMT, such as BPL-003 (intranasal mebufotenin benzoate) and GH001.

BPL-003 (Mebufotenin): An open-label Phase 2a study (NCT05660642) investigated a two-dose induction regimen (8 mg followed by 12 mg two weeks later) in patients with Treatment-Resistant Depression (TRD).⁷ This study demonstrated that the second dose at Week 2 led to further clinically meaningful reductions in MADRS scores, indicating that an induction strategy has the potential to deepen the clinical response beyond a single administration.⁷ These rapid, clinically meaningful effects were sustained for up to 3 months following the initial dose.⁷ This three-month durability achieved with the two-dose regimen is a crucial piece of evidence, suggesting that while the ultra-short intervention provides rapid relief, maintaining the response may require an intermittent, flexible re-dosing strategy, shifting the commercial model from a “one-time cure” to a recurring therapeutic solution.⁵

GH001 (5-MeO-DMT): Sponsor-reported Phase 2 data emphasises high remission rates (57.5% at Day 8).⁸ This programme also highlights a strategic commercial claim: the treatment requires no additional psychotherapy or therapist visits.⁸ This claim underscores the commercial focus on achieving efficacy based solely on the drug’s inherent properties, optimising logistical ease.

Large Phase 2 RCTs, such as NCT05870540 investigating BPL-003, are currently ongoing, and their results are anticipated to confirm the randomised, placebo-controlled efficacy data for pure 5-MeO-DMT in TRD.¹

Table 1: Efficacy and Quantitative Results from Controlled Trials of DMT-based Compounds

Compound/Formulation	Trial Phase/Design	Target Indication	Key Efficacy Metric (MADRS/Remission)	Effect Size (Cohen’s d) vs. Placebo	Durability of Effect	Source
Ayahuasca (DMT/Harmine)	RCT (NCT02914769)	MDD	Significant MADRS reduction at 2 hours	1.49 at Day 7 (Large)	Up to 21 days	⁶
BPL-003 (5-MeO-DMT analogue)	Phase 2a (Open-Label, 2-dose)	TRD	Enhanced MADRS reduction after 2nd dose	N/A (Open-Label)	Sustained up to 3 months	⁷
GH001 (5-MeO-DMT)	Phase 2 (Sponsor Data)	MDD/TRD	Remission rates 57.5% at Day 8	N/A (RCT data pending)	TBD	⁸

IV. Methodological Rigor and Confounding Biases in Psychedelic RCTs

To ensure the selection of robust evidence, it is necessary to critically assess the methodological framework of psychedelic clinical trials, as recognised by experts in the field.

A. The Challenge of Maintaining Blinding in Psychedelic Trials

The primary methodological challenge is the difficulty in maintaining blinding or masking.⁹ Because DMT and 5-MeO-DMT induce an immediate and profound subjective experience described as an intense alternate reality or a near-death experience ¹⁰, participants receiving the active drug are likely to be de-blinded. This failure of masking introduces a high risk of bias, resulting in inflated estimates of the average treatment effect.⁹

B. Quantification of Expectancy and Placebo Inflation

The estimation of treatment effect sizes is likely inflated by high levels of patient response expectancy. Participants often enter these trials convinced of a positive outcome due to extensive public and media coverage.⁹ Expectancy contributes significantly to the placebo response. In the active arm, the observed effects are emphasised both by the direct treatment effects and a synergistic response between the drug and the participant’s conviction (expectancy $\times$ treatment response).¹⁸

This inflation is a quantified concern; experts suggest that in unmasked general medical RCTs, effect sizes can be exaggerated by approximately 0.56 standard deviations.⁹ Consequently, the extraordinary effect size of $d=1.49$ observed in the Ayahuasca RCT must be considered the maximum potential benefit, including both pharmacological and non-pharmacological contributions, necessitating a conservative adjustment for final regulatory approval projections.

Furthermore, while the development of ultra-fast treatments like GH001 emphasise the drug’s inherent efficacy and minimise the need for extensive psychotherapy ⁸, the general model of classic psychedelic therapy incorporates a strong element of preparation and therapeutic alliance.⁹ If the high expectancy bias—which is often enhanced by the therapeutic ritual—is a significant component of the observed total effect size, then removing the extensive psychological support proposed in the ultra-fast approach may inadvertently reduce the non-pharmacological component of the effect size in a fully blinded comparison.

C. Future Requirements for Statistical Robustness

To achieve statistically sound and regulatorily acceptable results, future large-sample RCTs must address these confounds rigorously.⁹ This includes routinely measuring and reporting both participant expectancy levels and the success rate of the blind (de-blinding rates). Researchers are urged to employ advanced methodological designs and publish pre-registered reports with detailed statistical analysis plans to ensure the true, drug-specific effect size can be reliably isolated from confounding factors.⁹ Given the intensity of the subjective experience, innovative active placebos that mimic the physiological effects (such as transient increases in heart rate and blood pressure ⁵) without inducing a full psychedelic state will be critical for maintaining blinding integrity in Phase 3 trials.

V. Safety, Tolerability, and Risk Management Protocols

A comprehensive assessment of DMT and 5-MeO-DMT viability requires a detailed review of their safety and tolerability profiles from clinical trials.

A. Short-Term Safety Profile (5-MeO-DMT)

The short-term safety and tolerability profile of 5-MeO-DMT formulations administered in clinical trials have generally been favourable.¹⁹ Acute adverse events (AEs) are predominantly mild and transient, resolving spontaneously.⁵ The most frequently reported AEs include anxiety, nausea, and headache.⁵

Crucially, the early clinical trials of 5-MeO-DMT have reported a robust tolerability record: no Serious Adverse Events (SAEs) have been documented, and no adverse events led to participant withdrawal or drop-out from the studies.¹⁹ The fact that adverse events are mild and resolve quickly is a major factor in the logistical viability of the ultra-short intervention, as it ensures that the time savings from the rapid onset are not negated by the need for extended post-treatment management of side effects.

B. Cardiovascular and Physiological Monitoring

Both DMT and 5-MeO-DMT are known to produce transient increments in blood pressure (BP) and heart rate (HR) during the acute experience.⁵ This predictable physiological response necessitates strict clinical protocols, including the mandatory and continuous monitoring of vital signs and ECG parameters throughout the acute phase of treatment.² Patient screening must therefore exclude individuals with severe pre-existing cardiac conditions.

C. The Critical Risk of Serotonin Syndrome and Drug Interactions

The most significant contraindication is the potential for drug-drug interactions, specifically the high risk of Serotonin Syndrome.¹⁰ Because DMT is structurally related to serotonin, co-administration with other serotonergic agents, particularly SSRIs or MAOIs, can lead to a potentially life-threatening accumulation of serotonin.¹⁰

This chemical constraint imposes mandatory safety protocols, including rigorous patient screening and the requirement for substantial washout periods for any patient currently taking standard antidepressant medication.¹⁰ This inherent safety requirement naturally guides the clinical focus toward high-unmet-need populations, such as TRD, where patients are often already refractory to existing pharmacological treatments and are therefore more likely to accept the required washout protocols.

While current trials report zero SAEs, it is acknowledged that serious adverse events (including worsening of depression or suicidal ideation) may increase in frequency as sample sizes expand in future Phase 3 trials.¹

Table 2: Safety Profile and Acute Adverse Events of 5-MeO-DMT (Based on Phase 1/2 Trials)

Safety Category	Observed Finding (5-MeO-DMT Clinical Trials)	Clinical Significance	Patient Management Implications	Source
Serious Adverse Events (SAEs)	None documented	High short-term safety; based on small sample sizes	Requires intensive monitoring and reporting in Phase 3	¹⁹
Common AEs	Anxiety, Nausea, Headache	Mild to moderate, spontaneously resolving	Managed through appropriate set, setting, and acute support	⁵
Cardiovascular Effects	Transient increase in BP and HR	Predictable, requires careful acute phase monitoring	Exclusion of patients with unstable cardiac conditions	⁵
Drop-out Rate	Zero reported due to intolerance	Demonstrates high acceptability of the acute experience	Validates the feasibility of the ultra-short duration model	¹⁹
Drug Interactions	High risk of Serotonin Syndrome	Absolute contraindication with concurrent SSRIs/MAOIs	Mandatory patient washout and rigorous screening	¹⁰

VI. Regulatory Landscape and Commercial Development Trajectory

The regulatory progression of 5-MeO-DMT analogues reflects a favourable commercial trajectory driven by the drug’s high potency and short duration.

A. Breakthrough Therapy Designation (BTD)

The FDA’s decision to grant Breakthrough Therapy Designation to BPL-003 for TRD in October 2025 constitutes a critical de-risking event.³ BTD recognises the potential for the drug to offer substantial improvement over existing therapies for a population with high unmet need, and it grants the developer intensive guidance and accelerated regulatory review.³ This designation transforms the development programme from a speculative research endeavour into a validated, expedited pathway targeting the multi-billion-dollar MDD/TRD market.²⁰

B. Phase 3 Readiness and Time-to-Market Projections

The successful completion of Phase 2 programmes, demonstrating rapid and sustained efficacy up to three months following the induction regimen ⁷, provides the foundation for definitive pivotal trials. Discussions with the FDA regarding the Phase 3 trial design are underway, with expected initiation of the trials in the first or second quarter of 2026.⁴ This timeline suggests a rapid progression toward potential market entry.

C. Commercialisation and Scalability of Ultra-Fast Tryptamines

The logistical advantage of the ultra-short-acting profile is its most compelling commercial asset. The 15–30 minute treatment window significantly enhances scalability and accessibility compared to treatments requiring 4–8 hours of sustained clinical support.⁵ By minimising the patient’s acute subjective experience time, 5-MeO-DMT development offers an efficient, single-day dosing regimen that requires less intensive therapeutic infrastructure and reduces the strain on limited trained personnel.

Furthermore, the duration of effect is critical for the long-term commercial model. The demonstrated three-month durability achieved with the two-dose regimen ⁷ is crucial for future commercial planning. If Phase 3 confirms the need for intermittent dosing (e.g., semi-annual or annual), the commercial model shifts from a single-transaction sale to a recurring revenue stream, which is highly favourable for sustainable biotechnology valuation.

VII. Conclusion and Expert Recommendations

DMT-based tryptamines, particularly the 5-MeO-DMT analogue BPL-003, have demonstrated a potent clinical signal validated by robust early trial data (Cohen’s $d=1.49$ for Ayahuasca) and favourable regulatory recognition via FDA Breakthrough Therapy Designation for TRD. These agents are strategically superior in terms of logistical feasibility due to their ultra-short, single-day dosing profile, offering rapid antidepressant effects and a favourable short-term safety record with zero reported Serious Adverse Events in early cohorts.

However, the interpretation of early efficacy data must be tempered by methodological realities. The high response expectancy and the inability to maintain a perfect blind in psychedelic trials likely inflate the reported effect sizes.

Expert Recommendations

Conservative Efficacy Modelling: Future strategic forecasts and financial modelling should conservatively adjust reported Phase 2 effect sizes by accounting for the potential inflation of up to 0.56 standard deviations, which is typical in unmasked trials. This is necessary to establish realistic expectations for the true pharmacological benefit in fully controlled comparisons.
Phase 3 Methodological Rigor: The design of pivotal Phase 3 trials must prioritise the integrity of the double-blind through the rigorous validation and implementation of sophisticated active placebos, specifically engineered to mimic the physiological transient effects of the drug while confirming the success rate of the blind via participant questionnaires.
Prioritisation of Maintenance Efficacy: While rapid efficacy is established, the primary focus of large-scale trials must shift to definitively validating the long-term durability and maintenance of the antidepressant effect. Optimal strategies for intermittent, flexible re-dosing regimens must be established to ensure the sustained clinical response required for long-term patient benefit and commercial viability.

Works cited

Psychedelics for major depression—From controlled research settings into broader clinical use – PMC
Study Details | NCT05870540 | BPL-003 Efficacy and Safety in Treatment Resistant Depression | ClinicalTrials.gov
Life Sciences and Beckley Psytech Announce U.S. FDA Breakthrough Therapy Designation Granted to BPL-003, Underscoring its Potential in Treatment-Resistant Depression
Beckley’s BPL-003 mebufotenin nasal spray for treatment-resistant depression gets Breakthrough Therapy designation – OINDP News
Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression | American Journal of Psychiatry
Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial – PubMed https://pubmed.ncbi.nlm.nih.gov/29903051/
Life Sciences and Beckley Psytech Report Positive Phase 2a Data Demonstrating Improved Outcomes with a Two-Dose Induction Regimen of BPL-003 in Patients with Treatment-Resistant Depression – BioSpace
GH Research R&D Update https://investor.ghres.com/static-files/68e55af4-a7da-499c-aa99-2e0656b6ab89
Blinding and Expectancy Confounds in Psychedelic Randomised … https://blossomanalysis.com/papers/blinding-and-expectancy-confounds-in-psychedelic-randomised-controlled-trials/
DMT: Side effects, facts, and health risks – MedicalNewsToday https://www.medicalnewstoday.com/articles/306889
Neuropharmacology of N,N-Dimethyltryptamine – PMC – PubMed Central https://pmc.ncbi.nlm.nih.gov/articles/PMC5048497/
Study Details | NCT02455258 | Dancing for Better Aging: Evaluating the Impact of a Dance/Movement Therapy (D/MT) Program for Older Adults | ClinicalTrials.gov https://clinicaltrials.gov/study/NCT02455258
Study Details | NCT03986489 | Mindfulness-based Dance/Movement Therapy for Chronic Low Back Pain | ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03986489
Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis | Neurology https://www.neurology.org/doi/10.1212/WNL.0000000000005345
Comparative effectiveness of disease-modifying therapies for highly active relapsing-remitting multiple sclerosis despite previous treatment – a systematic review and network meta-analysis https://pmc.ncbi.nlm.nih.gov/articles/PMC12335774/
Study Details | NCT02914769 | Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression | ClinicalTrials.gov https://clinicaltrials.gov/study/NCT02914769
BPL-003 for Treatment-Resistant Depression: New Positive Phase 2a Data
Expectancy in placebo-controlled trials of psychedelics: if so, so what? – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC9481484/
Short-term safety and tolerability profile of 5-methoxy-N,N … – Frontiers
Cantor Fitzgerald reiterates Overweight rating on Cybin stock – Investing.com UK https://uk.investing.com/news/analyst-ratings/cantor-fitzgerald-reiterates-overweight-rating-on-cybin-stock-93CH-4306935

Parameter	Semmelweis Reflex	Doublethink	Cognitive Dissonance	Groupthink
Proponent(s)	Ignaz Semmelweis (mid-19th century)	George Orwell (1949)	Leon Festinger (1957)	Irving Janis (1972)
Focus	Immediate rejection of proposals, ideas or new knowledge.	Internalised control and often maintained by external pressure.	Internal conflict	Group conformity
Source of Tension	Probably none unless the above return in which case cognitive dissonance may emerge.	Contradictory thoughts imposed from outside and often accepted.	Conflicting ideas within an individual or group minds	Pressure to maintain group harmony
Level of Tension	None – as nothing to consider immediately after rejection.	Suppressed, may manifest indirectly	High, consciously felt	Varies – can be high for dissenters, low for those conforming
Risk or advantage to individual or organisation	Stagnation, missed opportunities	Loss of critical thinking, vulnerability to manipulation	Potential for growth if dissonance is addressed constructively and not defensively – else risk worsens	Suppression of individuality; potential for harmful choice.
Risk to Society	Impedes progress, can harm others (e.g. ignoring medical advances)	Fuels authoritarianism, large-scale manipulation	Can lead to irrational behaviour	Leads to flawed decision-making, erosion of ethics
Mitigation	Critical evaluation of evidence, willingness to change course – if ideas return.	Resisting indoctrination, fostering independent thought	Self-awareness, open-mindedness, seeking diverse perspectives	Encouraging dissent, establishing processes for questioning assumptions
Resolution	Often requires a crisis or overwhelming evidence to break through resistance	Requires breaking free of external control which can be incredibly difficult	Changing beliefs/behaviour, finding new information or justifications to align with actions	Challenging group norms, breaking cohesiveness, can involve confrontation, ostracism, or the group dissolving

Stage	Cost/Price (£)	Tax/Duty (£)	Tax/Duty Type	Calculation	Calculation
1. Manufacturer’s Cost	2	0	N/A	This is a hypothetical cost of production.
2. Specific Duty Added	2	5.89	Specific Duty	£294.72 per 1000 cigarettes / 1000 * 20	Fixed amount per pack.
3. Manufacturer’s Profit	7.89	0	N/A	(Assumed to bring the total to £7.89)	This is a hypothetical profit margin.
4. Ad Valorem Duty Included	9	1.11	Ad Valorem Duty	16.5% of £9.00 (approx. retail price before VAT)	Included within the retail price, not added separately.
5. Retailer’s Profit	10.11	0	N/A	(Assumed to bring the total to £10.11)	This is a hypothetical profit margin.
6. Final Retail Price (excl VAT)	13	0	N/A	(Includes specific duty and ad valorem duty)	This is the price displayed on the shelf, excluding VAT.
7. VAT Added	13	2.6	Value Added Tax (VAT)	20% of £13.00	Applied at the point of sale.
Total	15.6	9.6	Approximately 61.5% of the final price (£15.60) is tax – due to the simplified conservative assumptions about manufacturer and retailer costs and profit margins.

Documentation Issue	Critique
Vague Descriptors	Terms like “distressed state,” “emptiness,” and “intense anger” lack specific behavioural anchors. The descriptions are mere observations without any real substance. How was the intensity of the anger manifested? What did the patient say? How did she appear? Was she grimacing? Without concrete examples, these descriptors are open to interpretation and do not provide a clear picture of the patient’s presentation.
Generalised Interventions	Phrases like “explored coping mechanisms” and “discussed strategies” are so general that they amount to padding. No one will know what specific coping mechanisms were explored. How did this worker actually attempt to help the patient? What exact strategies were discussed? How were these tailored to the patient’s individual needs and the nature of their emotional instability?
Lack of Measurable Outcomes	The record mentions the patient feeling “slightly calmer” but lacks objective measures to assess the effectiveness of the interventions. How was this improvement gauged? Is it just ‘your’ word for saying so? Many services will accept such records as ‘standard’ because of cultural norms.
Ambiguous Plan	The plan to “continue to work on developing skills” and “encourage the patient to practice techniques” is vague and lacks specific, measurable goals. What specific skills will be targeted? What techniques were discussed ‘between sessions’? How will progress be monitored? What constitutes “practice” in this context, and how will adherence be assessed?
Omission of Risk Assessment	Given the nature of EUPD and the potential for self-harm, the record should include a formal risk assessment. What specific risk factors were considered? How was the risk of self-harm evaluated and managed?
Limited Patient-Specific Insight	While the record mentions EUPD, it does not provide specific insights into how this diagnosis informs the interventions or the plan. How were the chosen strategies tailored to the patient’s unique challenges related to their personality disorder?

Cognitive Activity	Description
1. Information synthesis	Gathering and integrating diverse information; evaluating reliability and relevance of each piece
2. Evidence evaluation	Critically assessing quality and strength of available evidence; identifying gaps
3. Principle balancing	Weighing competing ethical principles; reconciling guidelines with case-specific considerations
4. Stakeholder consideration	Analysing individual patient needs/rights; considering regulatory and societal requirements
5. Consequence projection	Anticipating potential outcomes; assessing short-term and long-term consequences
6. Risk-benefit analysis	Systematically evaluating risks; weighing risks against potential benefits
7. Legal framework integration	Incorporating relevant legal standards; ensuring compliance with statutory obligations
8. Ethical reasoning	Applying ethical frameworks; resolving ethical dilemmas in forensic psychiatric practice
9. Interdisciplinary integration	Synthesising perspectives from various disciplines; reconciling conflicting viewpoints
10. Decision refinement	Iteratively reviewing and adjusting decisions; fine-tuning to address all relevant factors
11. Uncertainty management	Acknowledging areas of uncertainty; developing mitigation strategies
12. Prioritisation	Determining relative importance of factors; focusing on critical elements
13. Cognitive bias recognition	Identifying potential biases; implementing strategies to minimise their impact
14. Justification formulation	Developing clear, logical rationale; ensuring transparent and defensible reasoning
15. Contextual adaptation	Tailoring approach to specific case factors; recognising unique case influences