Novel Treatment Approaches for Substance Use Disorders: Therapeutic Use of Psychedelics and the Role of Psychotherapy

The paper is a narrative review drawing on historical reports, observational and epidemiological studies, recent clinical trials and conceptual neurobiological models. The extracted text does not present an explicit, reproducible search strategy, inclusion/exclusion criteria, dates or databases searched, so it should be read as a conceptual synthesis rather than a systematic review or meta-analysis. Koslowski and colleagues concentrate their appraisal on two psychotherapy traditions—psychodynamic approaches and CBT—because these have the largest empirical footprint in the psychedelic literature and illustrate important conceptual differences. The review integrates descriptions of trial protocols used in contemporary studies (preparation, controlled dosing sessions, integration), examples of psychotherapeutic elements embedded in SUD trials, neurobiological theories (for example predictive processing and the REBUS model), and phenomenological features of the subjective psychedelic experience that have been linked to outcomes. Where trial designs are discussed, the authors describe common features (set and setting, dosing ranges, session structure) and note methodological limitations reported in the primary literature rather than conducting quantitative pooling or formal risk-of-bias assessment.

Historically, psychedelics were used both in indigenous rituals and in mid-twentieth-century clinical practice. The authors report that between the late 1950s and early 1970s approximately 40,000 patients with various psychiatric disorders received psychedelic treatments in clinical contexts, often with narrative reports of substantial clinical benefit. Contemporary clinical research has resumed since the 1990s and includes trials for depression, anxiety in terminal illness, tobacco and alcohol use disorders, OCD and suicidality. Recent trials have generally adhered to a common protocol model with three phases: preparation, one to four supervised dosing sessions spaced weeks apart, and integration. Typical dosing examples cited are moderate-to-high ranges such as LSD ≥ 200 μg or psilocybin ≥ 20 mg for peak-experience paradigms; earlier psycholytic approaches used repeated low-to-moderate doses (about 50–200 μg LSD). Across SUD trials, some studies embedded manualised CBT elements in preparation and integration (for example target quit dates, quit contracts, diaries and brief behavioural tools in smoking cessation studies; Motivational Enhancement Therapy in alcohol trials). Control conditions in recent trials have varied and include low-dose psychedelics, niacin, methylphenidate as an active placebo, waiting-list controls and a double-dummy RCT comparing psilocybin with six weeks of an SSRI. Measured outcomes reported in the literature point to promising feasibility, safety and signals of efficacy for psychedelics in SUD, but many trials are small, often rely on self-referred, highly motivated participants, and face substantial blinding challenges, all of which the authors report as potential sources of bias. Regarding safety, when modern screening (for example excluding those with personal or family history of psychosis) and carefully controlled set and setting are applied, the risk profile for classic psychedelics in trials is described as very low. The extracted text states that in cited trials since 2011 no persisting psychotic reactions were reported, and addiction risk to classical psychedelics such as psilocybin and LSD is regarded as negligible. Nonetheless, challenging acute reactions (fear, anxiety) are common and can be dangerous outside controlled environments; vulnerable individuals may experience destabilisation. On mechanisms, the review summarises psychodynamic and CBT-oriented accounts. From a psychodynamic perspective, earlier psycholytic and peak-experience models reportedly facilitated free association, regression, catharsis, transference intensification, recovery of repressed memories and existential insight; these processes were posited to reduce neurotic defence mechanisms and enable corrective emotional experiences relevant to addiction. The authors note, however, that most early psychodynamic studies lacked rigorous methodology and relied on phenomenological case reports. Neurobiological frameworks are discussed as bridging psychodynamic and cognitive accounts. The REBUS model and related predictive processing ideas propose that psychedelics transiently reduce the precision weighting of high-level priors, permitting revision of rigid belief structures implicated in addiction and reward learning. The authors suggest this could reduce craving and compulsive drug-seeking by relaxing inflexible predictions, and that a post-acute 'neuroplastic window' of days to weeks may allow psychotherapeutic work to consolidate new learning. From a CBT standpoint, psychedelics are framed as facilitating experiential learning and weakening avoidance: destabilisation of maladaptive beliefs combined with mindful, non-avoidant engagement with aversive content can permit extinction-like learning or operant conditioning that reduces avoidance and supports behaviour change. The review cites empirical reports linking intensity of mystical-type or emotional breakthrough experiences to reductions in substance use in tobacco and alcohol trials. A post-session 'afterglow' lasting about 2–4 weeks—characterised by increased mindfulness and cognitive flexibility and potentially associated with elevated BDNF in humans—is described as a period when integration and psychotherapeutic interventions may be most effective, although causal links between neuroplasticity markers and clinical outcomes remain to be established. The authors also emphasise common factors in psychotherapy (therapeutic alliance, setting, ritual, meaning), noting that the psychedelic state’s heightened suggestibility and context sensitivity likely amplify these elements and contribute to outcomes across different psychotherapeutic orientations.

Koslowski and colleagues interpret the literature to mean that psychedelic-assisted interventions function primarily as substance-assisted psychotherapy: the pharmacological action enables and amplifies psychological processes that are central to therapeutic change. They argue that both psychodynamic and CBT frameworks offer plausible and partly complementary explanations for how psychedelic experiences can produce durable change in SUD, but that many of the experiential phenomena (for example deep insights, mystical-type experiences, emotional breakthroughs) are not uniquely classifiable to a single school of therapy. The authors acknowledge several important limitations of the evidence base: many classical psychodynamic studies had low methodological rigour and were largely observational; more recent trials are often small, include motivated and self-referred participants, and face difficulties with effective blinding and adequate control conditions. Mechanistic links—between subjective experience, putative neurobiological processes such as increased plasticity, and clinical outcomes—remain incompletely specified. Safety considerations are reiterated: careful screening for psychosis risk and attention to set and setting are essential. For future research and clinical practice, the authors recommend larger, better-controlled clinical trials with improved blinding, head-to-head comparisons of different psychotherapeutic adjuncts to psychedelic dosing, systematic investigation of dose and dosing frequency, and studies designed to identify predictors and moderators of response. They also suggest that the distinctive mechanisms of psychedelics could foster closer integration of psychopharmacological and psychotherapeutic approaches in psychiatry, particularly for SUD, but stress that more rigorous empirical work is needed to determine the optimal amount and type of psychotherapy, strategies for relapse prevention, and how best to translate these interventions into broader clinical settings.

The authors conclude that psychedelic therapy comprises a complex interaction of pharmacological and psychological processes and should be conceptualised as substance-assisted psychotherapy rather than a purely pharmacological treatment. While both psychodynamic and behavioural frameworks provide valuable perspectives on mechanisms and therapeutic techniques, many psychedelic-related therapeutic factors cut across traditional schools. To clarify efficacy, mechanisms and implementation—especially in SUD—larger trials with better blinding and control conditions, and systematic comparisons of psychotherapeutic approaches are required.