Topic starter
Through in-depth research into language models, we have identified scientific studies in which psilocybin or MDMA were used to treat various mental health conditions and disorders listed in the DSM-5, such as autism spectrum disorder, bipolar II disorder, major depressive disorder, treatment-resistant depression, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, anorexia nervosa, nicotine use disorder and alcohol use disorder.
Neurodevelopmental disorders
1. Research: There is limited clinical research. A small double-blind pilot study investigated MDMA-assisted psychotherapy for autism (adults with autism spectrum disorder and severe social anxiety). This study showed a significant reduction in social anxiety in the MDMA group compared with the placebo group. For other neurodevelopmental disorders (such as ADHD or intellectual disability), there are as yet no clinical studies involving MDMA or psilocybin. However, there is theoretical speculation that psychedelics may improve social interaction and mood in autism, but hard data are lacking.
2. Safety: In the aforementioned MDMA study involving adults with autism, the treatment was perceived as safe; no serious side effects occurred. This suggests that MDMA is well tolerated by this group in a controlled therapeutic setting. General physical side effects of MDMA (such as a temporary increase in heart rate, blood pressure and jaw clenching) were mild and transient. No safety data are yet available for psilocybin in neurodevelopmental disorders, but in general, psilocybin is not considered physically toxic when administered under professional supervision. Naturally, careful screening (e.g. for epilepsy or severe sensory hypersensitivity) is required in this group.
3. Therapeutic effect: In adults with autism, a clear reduction in symptoms of social anxiety was observed following MDMA therapy – anxiety scores fell sharply and this improvement persisted for months. The MDMA sessions led to greater openness and reduced social avoidance, indicating improved social functioning. For other neurodevelopmental disorders, the therapeutic effect and potential benefits remain unknown. There are anecdotal reports that microdosing psychedelics can sometimes improve concentration or mood, but this has not been scientifically substantiated for conditions such as ADHD.
4. Risks/Contraindications: In individuals with autism spectrum disorder, sensory overstimulation or unpredictable emotional reactions may occur during a psychedelic session. Thorough preparation and a low-stimulus, supportive environment are therefore crucial. No specific contraindications have been reported within this group of disorders, but as a general rule, comorbid epilepsy or medication interactions must be ruled out. In general, patients with a neurodevelopmental disorder who also exhibit psychotic features should be excluded from MDMA/psilocybin therapy, due to the risk of inducing psychosis (see below).
Schizophrenia spectrum and other psychotic disorders
1. Research: There is no therapeutic research that uses MDMA or psilocybin to treat primary psychotic disorders such as schizophrenia. Historically, classic hallucinogens have occasionally been studied to induce a “model psychosis”, but not as a treatment. Patients with schizophrenia spectrum disorders are systematically excluded from modern studies involving psychedelics. This is because these substances are more likely to do harm than good in such patients.
2. Safety: The use of MDMA or psilocybin in people with psychotic disorders is considered unsafe. Psychedelics can induce prolonged or acute psychosis in susceptible individuals. For example, it is known that psilocybin can trigger an acute psychotic episode in people with schizophrenia, which sometimes requires hospitalisation. Although MDMA has fewer hallucinogenic properties, its serotonergic and dopaminergic effects mean that it too can exacerbate delusions or paranoia in someone with a predisposition to psychosis. In short: in a controlled setting, administration would be ethically and medically irresponsible in the case of these disorders.
3. Therapeutic effect: There is no proven therapeutic effect of MDMA or psilocybin in schizophrenia or related disorders. On the contrary, the effects of psilocybin appear to mimic certain symptoms of schizophrenia (such as hallucinations and cognitive fragmentation). MDMA may briefly increase openness and empathy, but this is irrelevant as such patients are actually at risk of increased disorganisation and suspicion.
4. Risks/Contraindications: An absolute contraindication for psychedelics is a diagnosis of, or a family history of, schizophrenia or other psychoses. The risks include an exacerbation of psychotic symptoms or the triggering of a new psychotic episode. It has been reported that the use of psilocybin by patients with schizophrenia can cause acute psychotic episodes requiring hospitalisation. Furthermore, use could increase the burden of the illness and worsen its course. In short, MDMA and psilocybin are strongly discouraged in cases of psychotic disorders.
Bipolar and related mood disorders
1. Research: People with bipolar disorder have generally been excluded from previous studies on psychedelics due to the risk of mania. As a result, data is scarce. However, recent developments indicate cautious interest in certain subgroups. In 2023, a small open-label study was conducted among patients with bipolar II disorder experiencing a depressive episode, in which a single 25 mg dose of psilocybin was administered alongside psychotherapy. This pilot study showed encouraging results: most participants (15 patients) demonstrated a significant reduction in depressive symptoms after 12 weeks, with no evidence of mood dysregulation towards mania. This suggests potential for controlled use in bipolar II depression. For bipolar I disorder (with a history of mania/psychosis), no clinical trials involving MDMA or psilocybin have yet been conducted, given the safety concerns.
2. Safety: Great caution is advised. Psychedelics and empathogens are considered contraindicated in bipolar disorder, particularly due to the risk of mania. In the aforementioned bipolar II study, no manic episodes were triggered; there was no deterioration in mood or increase in suicidal ideation following psilocybin administration. This suggests that, under strict conditions, it may be safe for stable bipolar II patients. Nevertheless, it remains experimental. There are case reports of individuals with bipolar disorder who became acutely manic following recreational psilocybin use. For this reason, participants with a history of bipolar I disorder are generally excluded from studies. MDMA, with its strong serotonergic and stimulant effects, could also trigger mania or a rapid mood shift; whilst direct research on this is lacking, the theoretical risks make its use hazardous.
3. Therapeutic effect: Psilocybin shows promise for unipolar depression (see next section), and this appears to extend, at least in part, to bipolar depression (type II). In the small study of bipolar II depression, almost all participants showed a clinically significant improvement; many achieved remission from depression according to the criteria. Importantly, there was no increase in mood instability or suicidal ideation in this group. This suggests that psilocybin, under strict screening and supervision, may provide symptom relief during bipolar depressive episodes. MDMA has not been systematically investigated as an antidepressant, but given the euphoria and empathy it can induce, it could theoretically contribute to emotional breakthroughs in psychotherapy. However, there is a lack of robust data for patients with bipolar disorder.
4. Risks/Contraindications: Important: A history of mania or psychosis is considered a contraindication – patients are rigorously screened for this. The greatest risk is triggering a manic episode. This may manifest as disinhibition, impulsive risk-taking behaviour or psychotic symptoms. Cases of mania following psilocybin use have been reported in patients with bipolar disorder, including those with bipolar II disorder. Furthermore, patients usually have to discontinue their mood stabilisers or antidepressants prior to psilocybin research, which in itself carries risks. MDMA use in bipolar disorder is particularly risky due to the likelihood of a mood shift towards (hypo)mania, and the acute onset of a serotonin dip afterwards, which could worsen the mood. In summary: the use of MDMA/psilocybin in bipolar disorder remains experimental and should only be considered in strictly supervised research settings. Its use outside a research context is not recommended.
Depressive disorders
1. Research: In recent years, a relatively large amount of research has been carried out into unipolar depression, focusing primarily on psilocybin. Various clinical trials (open-label and randomised) involving people with moderate to severe depression or treatment-resistant depression (TRD) show that psilocybin, administered in 1–2 high doses alongside psychotherapeutic support, leads to significant reductions in depression scores. For example, a randomised study in major depression found that psilocybin (a single 25 mg dose) significantly reduced depression compared with placebo (active placebo niacin), with an average difference of over 12 points on the MADRS scale in favour of psilocybin after 6 weeks. In a large phase 2 trial of treatment-resistant depression, ~30% of patients achieved full remission three weeks after a single psilocybin session. Some participants also reported improved functioning and quality of life. Although MDMA has primarily been studied for PTSD, not depression, some PTSD studies have also included depression scales on which improvements were likewise observed following MDMA therapy. However, no direct MDMA studies focusing on depression have been published.
2. Safety: Psilocybin therapy for depression is generally described in studies as safe and well tolerated. No serious side effects occurred in controlled settings. However, mild to moderate, transient side effects are often reported during or shortly after the session, including headaches, nausea, dizziness or a temporary rise in blood pressure. These side effects occur in approximately 60–80% of participants, but did not require medical intervention. MDMA has not been explicitly tested in patients with depression, but based on other research we know that MDMA-assisted therapy is generally easy to monitor medically; common acute effects include an increased heart rate, mild hyperthermia, jaw clenching, etc., which are usually mild. However, for safety reasons, patients must not have any contraindicating medical conditions (e.g. severe heart disease) and must not be taking any contraindicated medication (SSRIs and MAO inhibitors must be discontinued to prevent serotonin syndrome).
3. Therapeutic effect: Psilocybin demonstrates rapid and significant symptom reduction in depression. Patients often report a dramatic improvement in depressive mood and anhedonia within 1 day to 1 week. In some patients, the effect persists for several weeks to months after one or two doses, particularly when combined with psychotherapy. For example, in the TRD study, after three weeks, significantly more psilocybin patients met the criteria for response or remission than placebo patients. Many patients describe insightful or “spiritual” experiences during the session, which lead to new perspectives on themselves and their depression. This can result in breaking free from entrenched negative thought patterns and improved emotional processing. MDMA has not been proven to be an antidepressant, but in PTSD treatment, a reduction in depressive symptoms was sometimes observed as a secondary effect. Theoretically, MDMA could help by promoting positive emotional experiences and empathy, which may be beneficial in the treatment of patients with depression who experience significant shame or social isolation. However, this remains speculative without direct research.
4. Risks/Contraindications: In cases of depressive disorders, a number of risks must be taken into account. Firstly, careful selection is required: patients with psychotic features or a history of manic episodes are excluded, as psychedelics can be dangerous for them. Secondly, the experience can be intensely emotional – some patients with depression may experience brief bouts of heightened anxiety, sadness or a confrontation with repressed trauma during the psilocybin session. This is part of the therapeutic process, but requires a safe setting with trained therapists. Following the acute experience, there may be a vulnerable period (the “after-effects” days), during which proper support is needed to monitor suicidal impulses or disappointment (for example, if a cure does not occur immediately). However, the studies did not observe any exacerbation of suicidality immediately following psilocybin administration. Indeed, no serious adverse events relating to self-harm occurred in clinical trials. Nevertheless, clinicians must remain alert to suicidal thoughts during follow-up. A practical point is that patients must be free of psychotropic medication (e.g. SSRIs must be tapered off) before psilocybin is administered, to prevent interactions. This may temporarily lead to withdrawal symptoms or a relapse of depression, which must be taken into account in the risk assessment. In summary: for unipolar depression, MDMA and psilocybin show great promise, provided they are administered by specialist teams with due attention to exclusion criteria and aftercare.
Anxiety disorders
1. Research: The use of classical psychedelics to treat anxiety disorders is on the rise, but most research to date has focused on existential anxiety associated with serious illness. Psilocybin, in particular, has been tested in clinical trials on patients with anxiety and depression resulting from a life-threatening condition (such as metastatic cancer). These studies demonstrated a significant and rapid reduction in anxiety following a single supervised dose of psilocybin. For example, a single psilocybin treatment led to a marked reduction in anxiety and an improved quality of life in the majority of these patients. For primary DSM-5 anxiety disorders (such as panic disorder, social anxiety disorder or generalised anxiety disorder), research is more limited but ongoing. There is open-label evidence and case reports suggesting that psilocybin may be beneficial for OCD (obsessive-compulsive disorder, see separate chapter) and social anxiety. MDMA has been investigated for social anxiety in autism (described under neurodevelopment), and a small RCT has been conducted for anxiety associated with life-threatening illness. In that pilot study (n=18), MDMA was used in people with a serious illness and associated anxiety; MDMA proved to be well tolerated and resulted in a reduction in anxiety scores compared with placebo, although the difference was not statistically significant due to the small sample size. This suggests a possible effect, but requires further research on a larger scale. In general, large-scale research specifically into classic anxiety disorders is still lacking, but the initial results offer hope that psychedelics can reduce anxiety in a therapeutic context.
2. Safety: In the contexts studied (palliative care patients, social anxiety in people with autism, etc.), psilocybin and MDMA have been found to be safe under controlled conditions. No serious physical or psychiatric complications have been reported in these trials. However, the acute experience can be intense, particularly for anxiety-prone individuals: a temporary increase in anxiety or panic during the trip does occur. For example, some cancer patients experienced brief episodes of existential anxiety or sadness during the psilocybin session, before their overall anxiety levels decreased. With proper preparation and supervision, this is usually managed and leads to emotional processing. Physiologically, the substances are reasonably safe in healthy individuals; MDMA can cause a short-term increase in heart rate and blood pressure, which is potentially risky in cases of untreated serious cardiac conditions. For this reason, screening for cardiovascular disease is carried out beforehand, and such patients are excluded. Psilocybin has few effects on the autonomic nervous system, but anxious individuals may develop a stress response (high blood pressure, hyperventilation) if the experience is overwhelming. This is why a medical setting and monitoring of vital signs are recommended. In general, studies report that both psilocybin and MDMA, when administered at therapeutic doses, are relatively safe and well tolerated by anxious patients, provided they are under the direct supervision of professionals.
3. Therapeutic effect: In cases of anxiety disorders, psychedelics can lead to a significant reduction in anxiety and behavioural change, often by addressing underlying causes. In cases of terminal anxiety (palliative care patients), a psilocybin session was found to result not only in reduced anxiety, but also in reduced depression and greater acceptance of the situation. These effects occurred rapidly (within days) and, in many cases, persisted for months, coinciding with mystical or insight-giving experiences reported by patients. In cases of social anxiety (such as in adults with autism), MDMA therapy showed a dramatic reduction in social fear and avoidance. Following MDMA sessions, participants felt more open, more confident in social situations and less anxious when initiating contact. Although direct research into conditions such as panic disorder or GAD (generalised anxiety disorder) is still scarce, there are reports that some patients, following psychedelic therapy, break through their avoidance behaviour and that persistent anxiety patterns are disrupted. MDMA is known for inducing a sense of safety and trust, which can be particularly helpful in cases such as social phobia or trauma-related anxiety (more on this below). All in all, the available data suggest that MDMA and psilocybin have the potential to effectively alleviate anxiety symptoms – both through acute reduction in anxiety and by facilitating new perspectives and emotions, thereby enabling clients to move beyond being paralysed by their anxiety.
4. Risks/Contraindications: Anxiety disorders do not in themselves constitute a strict contraindication, but there are points to bear in mind. Firstly, any comorbid conditions must be taken into account: someone with severe depression or personality disorders alongside their anxiety requires extra care (and may be better treated with alternative methods first). Secondly, one must be mindful of acute panic reactions: a patient with panic disorder may, in theory, experience intense panic during the peak of psilocybin’s effects. For this reason, the set (mental state) and setting (safe environment) are arranged in such a way that the person can be reassured should this occur. Unsupervised use of psychedelics by patients with anxiety is downright dangerous due to the risk of a panic attack or dissociation. Furthermore, a fear of heights, claustrophobia, etc., are not directly relevant during the session (as those situations do not arise), but the inner experience may evoke images or feelings that are anxiety-inducing. Therapists are trained to talk the person through these experiences. Contraindications mainly apply if there are psychotic features associated with the anxiety disorder (for example, a psychotic variant of OCD or PTSD – in which case exclusion applies, as discussed earlier). Serious medical conditions (unstable angina pectoris, recent stroke) are also general contraindications, as the anxiety or physical response during the session could place an excessive strain on the individual’s condition. In summary: for pure anxiety disorders, MDMA and psilocybin can be safe and effective under therapeutic supervision, provided that practitioners are prepared for temporary anxiety flare-ups during the session and the patient is well supported afterwards.
Obsessive-compulsive and related disorders
1. Research: Obsessive-compulsive disorder (OCD) is a particularly difficult-to-treat anxiety disorder, for which psychedelics are now also being explored. Small-scale research involving psilocybin has shown promising results. In an open-label pilot study, 9 patients with treatment-resistant OCD were given psilocybin (at varying doses) and, in all participants, compulsive symptoms (measured using the Y-BOCS score) decreased shortly after administration, in some cases very dramatically (23–100% acute symptom reduction). More recently (2023), a randomised pilot study involving 15 adults with severe OCD was presented at a conference: they received multiple doses of psilocybin over 8 weeks (compared with the control medication lorazepam). Outcome: psilocybin led to a significant reduction in OCD symptoms compared with the control group. After the full dosing phase (8 weeks), 80% of the psilocybin group showed a clinically relevant improvement (>25% reduction in symptoms), of whom 40% were even in complete remission from their OCD symptoms. At a 6-month follow-up, ~67% were still showing a clear improvement (and ~20% were in remission). These are impressive figures for such a persistent disorder. For related disorders (such as body dysmorphic disorder or trichotillomania), research is scarce; a single case report and a small open-label study also suggest possible improvement following psilocybin in these conditions, but the data are very limited. MDMA has not been systematically investigated in OCD, and there is little reason to assume that it would have much effect here, given that OCD is less about emotional processing and more about repetitive thoughts. Most attention is therefore focused on psilocybin (and other classic psychedelics) in OCD.
2. Safety: Psilocybin treatment in OCD patients appears to be well tolerated. The study described reported that psilocybin did cause temporary side effects (such as sensory disturbances during the trip), but no serious side effects occurred. Importantly, no increase in suicidal ideation or psychotic symptoms was observed in the OCD patients who received psilocybin. This is relevant because there were prior concerns that psychedelics might exacerbate obsessive thoughts or lead to psychosis – this does not appear to be the case in a therapeutic context. Even at high doses, it remained safe under supervision. Furthermore, the participants were often on SSRI medication, which was tapered off prior to the study; despite this withdrawal phase and the drug itself, there were no alarming adverse effects. There is a lack of MDMA data in OCD, but there is no specific reason to assume that MDMA would be physically less safe than in other groups: general MDMA risks (increased heart rate/blood pressure, dehydration if not properly hydrated) also apply here, but these are manageable under medical supervision. One point to note in OCD is that many patients take benzodiazepines or antidepressants; these often need to be paused before a psychedelic session (so as not to block effects or avoid interactions). This must be done safely to prevent rebound anxiety or epileptic seizures (during benzodiazepine withdrawal). In a research setting, this is carried out under supervision, which enhances safety. In general, it can be said that psilocybin therapy has proven to be safe in the OCD studies conducted to date.
3. Therapeutic effect: Initial results suggest that psilocybin may have a significant and long-lasting therapeutic effect on OCD symptoms. Patients often report that, immediately after the session, their obsessive thoughts cease or their urge to perform compulsions is greatly reduced. In the research setting, this was quantified: one week after the final dose, 80% of the participants showed at least a quarter reduction in their OCD score, with nearly half of them in complete remission. Some of these improvements lasted for months, particularly among those who received multiple sessions. The mechanism is thought to be that psilocybin breaks through entrenched thought patterns and leads to increased cognitive flexibility. OCD is characterised by rigid, repetitive neural networks; psychedelics appear to temporarily reorganise connectivity in the brain, which patients describe in their own words as “being able to pause their thoughts” and “zooming out from their own obsessions”. In addition, OCD patients in studies often reported reduced anxiety and relief from comorbid depressive symptoms following psilocybin treatment. This points to a broad positive effect on well-being. Although the number of participants studied is small, the effect sizes are striking and suggest that psilocybin therapy for OCD could lead to a significant reduction in symptoms and possibly even recovery where conventional treatments fall short. Naturally, further research (larger RCTs) is needed to confirm this.
4. Risks/Contraindications: One advantage in the case of OCD is that these patients are rarely primarily psychotic; the risk of triggering a psychosis is therefore low, but one must remain alert to any schizo-obsessive variants (patients with both OCD and schizophrenia, who would be excluded). In practice, there are few specific contraindications for psilocybin in OCD other than the general ones (heart problems, epilepsy, pregnancy, etc.). On the contrary, psilocybin appears to work surprisingly well where SSRIs and exposure therapy fail. However, patients must, of course, be open to this intensive form of treatment; severe personality disorders or unstable living conditions may constitute a relative contraindication, as these can make it more difficult to integrate the experience. Furthermore, care must be taken to taper off regular medication in advance to prevent serotonin syndrome and effect masking – this must be done under medical supervision to prevent relapse. A potential risk is that some OCD patients may react by wanting to exert control during the trip (resistance). This can lead to moments of anxiety if the patient resists the effects. Good psychological support is crucial to help the person let go. Finally, as with other disorders, follow-up therapy and support must be available. OCD is a chronic condition, so it is possible that compulsions may increase again over time; without integrative therapy following psychedelic sessions, patients might become disappointed or feel they have failed, which could damage their morale. However, once again, no serious adverse outcomes have been reported – not even suicidal ideation or psychosis in these small studies. Consequently, the risks are currently considered to be low. Contraindications are largely the same as for anxiety disorders: do not use in individuals with underlying psychotic conditions, and observe physical contraindications. All things considered, psilocybin offers a potentially safe new approach to OCD, provided it is administered by experienced teams.
Trauma- and stressor-related disorders
(This mainly includes post-traumatic stress disorder – PTSD – and adjustment disorders.)
1. Research: MDMA-assisted therapy for PTSD is one of the most extensively studied indications in a research context. Six phase 2 studies and two large phase 3 trials have already been conducted in patients with chronic, treatment-resistant PTSD. These studies (sponsored by MAPS) unanimously show that MDMA, administered in combination with intensive trauma therapy, is highly effective for moderate to severe PTSD. In the first pooled Phase 2 analyses, ~54% of the MDMA group achieved clinical remission from PTSD (compared with ~23% in the placebo group) after two to three sessions. Even more convincingly, a second Phase 3 RCT (multicentre, n=104) has recently been completed: the results, published in *Nature Medicine* (2023), show that after three MDMA sessions, 71% of the participants no longer met the criteria for a PTSD diagnosis, compared with ~47.6% in the placebo + therapy group. The difference is highly significant both statistically and clinically, confirming that MDMA-assisted therapy is almost twice as effective as trauma therapy without MDMA for treatment-resistant PTSD. These findings are consistent across various subgroups, including different types of trauma. Based on this robust research, MDMA-assisted psychotherapy has been designated a “Breakthrough Therapy” by the FDA, and approval in the US is expected in 2024. Considerably less research has been conducted into psilocybin for PTSD. However, initiatives are underway: for example, the first RCT comparing psilocybin-assisted psychotherapy with a placebo in PTSD patients began in 2022. The results of this trial are not yet known. Theoretically, psilocybin could also help with trauma processing, but many consider MDMA to be more suitable due to its empathogenic nature. Other trauma- or stress-related disorders (such as acute stress disorder, complex PTSD, or adjustment disorder) have scarcely been studied specifically; however, it is expected that findings relating to PTSD will be partially applicable to these conditions.
2. Safety: MDMA therapy for PTSD appears to be relatively safe and well tolerated, despite the high-risk nature of the patient group. In the phase 3 trials, no serious adverse effects attributable to MDMA occurred. In other words, no life-threatening medical complications were observed, nor were there any persistent psychiatric problems. The most common side effects of MDMA in this context were similar to previous findings: mild to moderate nausea, muscle tension (e.g. jaw clenching), sweating, and an increase in blood pressure and heart rate during the session. These reactions were generally temporary and subsided in the days that followed. Importantly, MDMA often made patients more emotionally stable in the weeks following the sessions – no increase in suicidal behaviour was observed in the MDMA groups; on the contrary, some patients with severe PTSD saw their suicidal tendencies decrease in parallel with an improvement in symptoms. It should be noted, however, that occasional short-term increases in suicidal ideation were reported whilst processing trauma, in both MDMA and placebo treatment groups; however, no suicidal acts were carried out and the causal link with the drug is unclear. From a physical perspective, MDMA therapy requires monitoring: PTSD patients may have comorbid hypertension or heart problems, so screening is necessary. In the studies, vulnerable patients (e.g. those with an unstable medical condition) were excluded, and under those circumstances, MDMA was medically manageable. Even in PTSD patients with the dissociative subtype (who are often considered difficult to treat), MDMA therapy proved safe: there was no worsening of dissociation or psychotic symptoms. Psilocybin’s safety profile in trauma is less clear due to a lack of data; however, from research involving anxious cancer patients (who often experience trauma-like stress), we know that psilocybin is also well tolerated, with similarly mild side effects (temporary anxiety, elevated blood pressure). General psychiatric contraindications (such as active psychosis, uncontrolled substance dependence) also applied in PTSD studies. In summary, it can be stated that, provided it is administered under strict protocols, MDMA-assisted therapy for PTSD has been found to be safe, even for severely traumatised individuals.
3. Therapeutic effect: The therapeutic effect of MDMA on PTSD is exceptionally significant compared with traditional treatments. As mentioned, research shows that over two-thirds of patients achieve complete remission or a very marked improvement in PTSD symptoms. This is striking because the study populations were generally treatment-resistant (having usually suffered from PTSD for years despite other therapies). MDMA works by creating a state of emotional safety, empathy and insight during the session, in which patients can confront their traumatic memories without being overwhelmed by fear. Therapists report that patients often experience profound breakthroughs whilst under the influence of MDMA: they are able to relive and re-evaluate traumatic events with self-compassion, often leading to genuine trauma resolution rather than avoidance. The substance reduces the “fight-or-flight” response – anxiety and defensiveness decrease – whilst the ability to talk about the trauma increases. This results in a dramatic reduction in PTSD scores (e.g. the CAPS-5 symptom score fell by ~30 points compared with ~13 points in the placebo group for dissociative PTSD). Many patients no longer meet the diagnostic criteria after treatment (71% MDMA vs 47% placebo in the latest trial), meaning that their lives are no longer dominated by trauma. In addition to the core symptoms (re-experiencing, avoidance, arousal), comorbid symptoms such as depression, anxiety and functioning in daily life often improve as well. Some participants report “feeling true peace for the first time” or that they have been able to come to terms with the trauma. Moreover, this effect appears to be long-lasting: follow-ups up to 12 months after MDMA therapy showed that most improvements are maintained or continue to consolidate. This suggests that MDMA does not merely suppress symptoms, but initiates a therapeutic healing process (in combination with psychotherapy) that continues to have an effect. Psilocybin could, in theory, also be helpful in treating trauma by offering new perspectives and a sense of meaning; some case studies suggest that a “mystical” experience induced by psilocybin can help people reinterpret their trauma. However, hard data on this is still lacking, and ongoing studies must determine whether psilocybin will play a role alongside or in place of MDMA in the treatment of PTSD. Nevertheless, it is clear that MDMA therapy is currently the most promising new treatment for PTSD, with unrivalled effect sizes.
4. Risks/Contraindications: Despite the successes, there are certainly risks that must be taken into account. Reliving trauma during therapy is an intense experience – if this does not take place in a controlled setting, it can destabilise patients or re-traumatise them. Therefore, MDMA or psilocybin should never be used to treat trauma without supervision. People with PTSD often need a stabilisation phase first; “digging deep” straight away with a psychedelic without having developed coping skills can be dangerous. This means that patients who are acutely suicidal or severely dissociative/undifferentiated are (for the time being) not suitable candidates. For example, psychedelic therapy is not recommended during the acute phase following trauma or for someone with uncontrolled impulsivity, until greater stability has been achieved. Furthermore, any comorbid medical conditions must be considered contraindications: for example, many PTSD patients have a history of alcohol or drug abuse; active addiction must be addressed before MDMA is used, otherwise the setting is not safe. Cardiovascular problems must also be stabilised (MDMA can exacerbate cardiac arrhythmias). A specific subgroup is PTSD with dissociation (the derealisation/depersonalisation subtype). Fortunately, analysis shows that even this group benefits significantly from MDMA (a reduction in symptoms comparable to that seen in non-dissociative patients), which could represent an important niche. Nevertheless, it requires extra attention because these patients tend to “disappear” into dissociation when under stress. During MDMA sessions, therapists must pay close attention to grounding techniques if the patient becomes detached or experiences a change in consciousness. In addition, MDMA (and, to a lesser extent, psilocybin) carries a risk of temporary physical side effects: increased blood pressure, tachycardia and elevated body temperature. This can place a strain on the often middle-aged PTSD population; medical monitoring during the session is therefore mandatory. Cases of short-lived cardiac arrhythmias (extrasystoles) have been reported during MDMA sessions, but these were self-limiting. Patients must be closely monitored between sessions – MDMA can cause a mild dip in mood for a few days afterwards (“sugar crash”), which requires attention in a vulnerable group. Fortunately, trials show that MDMA therapy does not lead to increased substance misuse: participants did not start using MDMA recreationally on a large scale. Nevertheless, the risk of psychological dependence remains in theory (the desire to experience that sense of safety over and over again). That is why integrative therapy is crucial, so that the patient learns to build that sense of security within themselves rather than through the substance. Finally: absolute contraindications within this category include active psychosis, bipolar disorder, severe cardiovascular disease and untreated epilepsy, in line with the general exclusion criteria. In short, provided these precautions are observed, the benefits of MDMA/psilocybin for PTSD clearly outweigh the risks: the treatment has been assessed by the FDA as safe enough to be likely to be approved for clinical use.
Dissociative disorders
(For example, dissociative identity disorder (DID), depersonalisation disorder, dissociative amnesia.)
1. Research: There is virtually no research into the use of MDMA or psilocybin specifically in relation to primary dissociative disorders. People with dissociative identity disorder (formerly known as multiple personality disorder) or chronic depersonalisation are generally excluded from psychedelic research due to the complexity and risks involved. Some PTSD studies did, however, include patients with dissociative symptoms (such as the dissociative subtype of PTSD in the MDMA study, see above). These studies suggest that MDMA-assisted therapy can be effective and safe even in the presence of dissociation. However, this concerned dissociation in the context of PTSD. There are no specific clinical trials focusing on DID/DIS or depersonalisation in their own right. At most, there are case reports within the therapeutic community suggesting that MDMA is sometimes used (for example, on the underground scene) to help people with DIS integrate different identities, but these are anecdotal and not documented in the scientific literature. Psilocybin or other classic psychedelics have not been studied in relation to DID – given the risk of exacerbating confusion, there is likely to be some reluctance to use them in this context.
2. Safety: It is not known whether administering MDMA or psilocybin to someone with a dissociative disorder is safe. In theory, MDMA might promote empathy and communication between different identity states, but there is also a risk that the boundaries between identities could become further blurred in an uncontrolled manner. In patients with DID, the psyche is often fragile and their sense of reality fluctuates, meaning that a psychedelic experience can be extremely disorientating. Furthermore, many of these patients are taking psychotropic medication (antidepressants, antipsychotics, etc.) which would need to be tapered off – this poses additional risks. In short: without a solid research basis, it is considered unsafe to administer psychedelic substances to this population. Even in the PTSD studies, the presence of a full-blown dissociative identity disorder was usually an exclusion criterion. Given the complex clinical presentation, safety is only conceivable with very intensive supervision by dissociation specialists.
3. Therapeutic effect: There is no proven therapeutic effect; only theoretical speculation. Some therapists suggest that, by reducing anxiety and boosting trust, MDMA could lead to a faster breakthrough in the treatment of trauma in DID – for example, enabling different alters to process trauma together in a single session. Similarly, psilocybin might potentially provide new insights into the origins of dissociation or promote a sense of unity in conscious experience. However, without studies, we do not know whether this is realistic. It is also conceivable that, in the case of dissociative disorders, psychedelics actually have little effect on the core symptoms (given that dissociation is a mechanism of separation that may be more difficult to influence). In the absence of research data, we cannot therefore claim any therapeutic effect.
4. Risks/Contraindications: Dissociative disorders are often associated with severe trauma and, in some cases, with psychotic micro-episodes; as a result, the risks are the same as, or even greater than, those associated with PTSD or psychotic disorders. A significant risk is that a psychedelic experience may trigger further uncontrolled dissociation. For example: a person with DID might slip completely into a different identity during the session or experience further fragmentation of their identity, which would exacerbate their suffering. The ability to distinguish reality from hallucination is already compromised in patients with dissociative disorders; psilocybin-induced hallucinations can further cloud this distinction and may result in a prolonged worsening of depersonalisation. Furthermore, suicidal ideation is often high in this group; an improperly supervised session that brings forgotten memories to the surface without sufficient integration may increase suicidal tendencies. It is therefore recommended that the use of MDMA as an adjunct should only be considered at a very advanced stage of therapy – once the patient has stabilised and a strong therapeutic alliance has been established – and even then, strictly within a research context. Contraindications therefore overlap with those for PTSD: untreated instability, active self-harm, and susceptibility to psychosis. In practice, the use of MDMA/psilocybin for primary dissociative disorders is currently experimental and potentially risky. Consequently, there are no standard treatment programmes for this, and this will remain the case until there is scientific evidence of safety and efficacy – something that is still years away, given the complexity of these disorders.
Somatic symptom disorders and related disorders
(E.g. somatic symptom disorder, hypochondria, conversion disorder.)
1. Research: For this category (mental disorders manifesting as physical symptoms), there is little to no research into MDMA or psilocybin as a treatment. The literature focuses primarily on anxiety, depression and addiction in relation to psychedelics, not on somatic symptom disorders. There are therefore no clinical trials that, for example, use psilocybin to treat medically unexplained pain or conversion attacks. At best, one finds isolated case reports of patients with psychosomatic symptoms who felt they had benefited from a psychedelic experience, but this is anecdotal. Scientifically, no evidence is currently available.
2. Safety: As there are no specific studies, safety is unknown; however, in the absence of contraindications, it would be reasonable to assume that MDMA or psilocybin do not, in principle, pose any additional physical risks to this population beyond the usual ones. However, patients with somatic symptom disorders may be overly focused on physical sensations – this can be problematic during a trip, as psychedelics actually heighten sensory perceptions. For example, someone with a somatic symptom disorder who is constantly aware of their heartbeat or stomach might, whilst under the influence, pay even more attention to those sensations and become more anxious. This means that, although the substances are pharmacologically safe (no particular organ toxicity), the experience can be psychologically challenging for this group. Not having any serious somatic comorbidities is a prerequisite for participation in psychedelic studies; so if someone is taking a lot of medication or undergoing medical procedures due to somatic obsessions, their condition would need to stabilise first. All in all, we can state that no known safety concerns have emerged – after all, no study has reported adverse events – but neither are there any specific safety data. Therefore, its use should only be considered within a research context and with rigorous medical screening.
3. Therapeutic effect: As yet unproven. Theoretically, one might speculate that psychedelics could help these patients gain insight into the underlying psychological factors behind their physical symptoms. For example, someone with conversion disorder (paralysis without an organic cause) might, through a psychedelic session, experience a repressed trauma or emotion that underlies the symptom. There are documented cases in the history of psychiatry where LSD therapy was occasionally used in the 1950s to treat so-called psychosomatic disorders, with mixed results (not systematically recorded). Psilocybin might, through neuroplasticity and introspection, break through rigid somatic preoccupations – for example, enabling a hypochondriac to realise that their anxiety is unfounded. But this is purely hypothetical. MDMA might, via its empathogenic effect, be therapeutically beneficial in somatic symptom disorder by increasing trust between patient and therapist and addressing any underlying trauma (which manifests somatically). However, without research, there is no proven effect. In short, at present there is no scientifically substantiated therapeutic effect of MDMA or psilocybin for these disorders.
4. Risks/Contraindications: One potential risk is that these patients may misinterpret physical sensations whilst on a trip. For example, someone with a fear of illness might experience the increased heart rate caused by MDMA and think they are having a heart attack, despite reassurance. This can lead to panic. Similarly, a conversion disorder patient on psilocybin may experience a temporary exacerbation of their symptoms (e.g. increased tremor or, conversely, new psychosomatic reactions) as an expression of underlying emotion. Therefore, the careless use of psychedelics in these individuals could also exacerbate their symptoms. Contraindications largely follow the general guidelines: severe heart problems (particularly relevant if the person also has actual physical symptoms), epilepsy, etc. It is also important that no acute somatic condition is overlooked: if someone actually has an undiagnosed physical illness, this must be ruled out before a session for safety reasons. Furthermore, if the patient is taking a significant amount of psychosomatic medication (such as painkillers, benzodiazepines or beta-blockers), the potential interactions with these must be considered. Benzodiazepines, for example, can reduce the effects of psychedelics, which is a problem from a therapeutic perspective (perhaps not an immediate danger, but it does reduce efficacy). In principle, there is no outright ban, but great caution is advised. Given the lack of evidence, the use of MDMA or psilocybin for somatic symptom disorders would currently be considered experimental and is more likely to entail risks (confusion, anxiety) than to offer clear benefits. Consequently, this is not a standard or recommended intervention outside the context of any future research.
Nutritional and eating disorders
1. Research: Very preliminary research into the use of psychedelics for eating disorders, particularly anorexia nervosa (AN), is beginning to emerge. For example, a recent phase 1 open-label study was conducted involving 10 women with anorexia nervosa (average BMI ~19.7, some of whom were in partial remission) to test the safety and feasibility of psilocybin therapy. The participants received a single session with 25 mg of psilocybin in a therapeutic setting. Results: the treatment was feasible and safe, with no serious side effects. No clinically significant abnormalities were observed in ECG patterns, vital signs or suicidal ideation following psilocybin administration. However, 2 out of 10 patients developed asymptomatic hypoglycaemia (low blood sugar) shortly after the session, which resolved spontaneously within 24 hours. This is relevant because, due to their low reserves, anorexia patients are susceptible to drops in blood sugar – the fact that this episode was mild and short-lived suggests that psilocybin is medically manageable in AN, provided it is administered under supervision. With regard to observations of effects: psychological outcome measures were examined on a trial basis. It was found that obsessions with weight and body shape decreased significantly after the psilocybin session – with a medium to large effect size – at both the 1-month and 3-month follow-up points. General anxiety also decreased markedly during the follow-up period. Depressive symptoms showed no significant average change in this small sample. Interestingly, 5 out of 10 participants showed a slight weight gain in the 3 months following the session (an increase of 0.4 to 1.2 BMI points), whilst the others remained stable – on average, weight did not change significantly, which is to be expected following a single session without explicit dietary intervention. Qualitative interviews from the same study indicated that most participants rated the psilocybin experience as helpful and acceptable; insights reported included a better understanding of the nature of their anorexia and the development of greater self-compassion. In addition to anorexia, an international Phase 2 trial by the company Compass Pathways using psilocybin for AN is currently underway (or has just been completed), the results of which are yet to be published. There is hardly any direct research into bulimia nervosa (BN) and binge-eating disorder; however, a recent review suggests that psychedelic-assisted therapy may be effective for both anorexia and bulimia. This is based on the limited preliminary work and on overlaps with addiction mechanisms (where psychedelics have also proved effective). MDMA is also attracting interest: there is an ongoing study (MAPS, “MED1”) examining MDMA-assisted therapy for anorexia (AN-R type), including the involvement of a care provider. However, no results from this study have been published to date. In summary: research is at an early stage, with psilocybin for anorexia leading the way, where the initial signs are promising in terms of safety and efficacy.
2. Safety: Eating disorders (particularly anorexia) are associated with physical vulnerabilities – malnutrition, electrolyte imbalances, bradycardia, osteopenia, etc. This makes safety a crucial consideration. The phase 1 study in patients with anorexia showed that psilocybin was well tolerated: as mentioned, there were no significant adverse effects on the heart, blood pressure or laboratory values, apart from two cases of transient hypoglycaemia. It is striking that no cardiac arrhythmias occurred, given that anorexia patients are often at risk of QT prolongation and arrhythmia due to electrolyte imbalances. Apparently, the patients studied were reasonably medically stable (BMI ~19, so not severely underweight at the time of dosing). This is important: the study confirmed that psilocybin is safe in patients with recovered or mild AN, but it says nothing yet about safety in those with a very low BMI (<15) – such patients might need to be somatically stabilised first. MDMA has not yet been clinically tested for anorexia, but it is expected that its stimulant effects (increased heart rate, blood pressure and body temperature) are potentially more risky for severely malnourished patients. Someone with active AN who is, for example, bradycardic or hypotensive, may experience a stress response to MDMA that puts excessive strain on the heart. Furthermore, MDMA can stimulate the release of vasopressin, which, in combination with dehydration in AN, can lead to fluid balance problems. This means that medical screening and monitoring for MDMA in eating disorders would be even more crucial. For psilocybin, therefore, the phase 1 trial showed no clinically relevant disruption of cardiovascular or metabolic parameters, which is a significant reassurance. All reported side effects were mild and transient. These included, during the session, the expected: temporary emotional lability, sensory disturbances, a slight increase in blood pressure – but not a single participant had to stop prematurely or required medical intervention. Conclusion on safety: psilocybin appears to be safe and well-tolerated in anorexia patients who have (somewhat) recovered physically. In cases of severe underweight or acute medical instability, it remains, of course, contraindicated until refeeding has taken place. From a psychiatric perspective, caution is also required: anorexia is often accompanied by comorbid depression, obsessive-compulsive disorder or autistic-obsessive traits; these patients were not excluded from the pilot study and experienced no problems. Nevertheless, actively suicidal or psychotic behaviour would constitute a contraindication, just as it does with other forms of psychedelic therapy.
3. Therapeutic effect: Although still preliminary, the signs are positive. In the psilocybin study for anorexia, patients reported mental changes that appeared to be therapeutically valuable. Particularly telling was the significant reduction in obsessions with weight and body shape one month and three months after the session. This suggests that psilocybin may help to reduce cognitive rigidity and preoccupation with weight and appearance – a core problem in anorexia. Anxiety levels also decreased following treatment, which is important because anorexia patients often experience intense anxiety around eating and weight gain. Some participants described how the psilocybin experience helped them realise how their entire identity had become entangled with the eating disorder, and that they were able to view this with greater compassion and flexibility. For example, one patient noted that after taking psilocybin she was “more willing to recover” but that her body was still lagging behind physically. This illustrates that her mindset had changed: motivation to recover can grow, even if the immediate effect on weight is not significant in the short term. In this regard, it is encouraging that half of the participants did show some weight gain within three months (small but in the right direction). Quality of life and functional impairment were also examined and appeared to improve, although the study was not specifically designed to assess these outcomes. For bulimia and binge-eating disorder, the effect remains to be seen – there is speculation that psilocybin could reduce cravings and self-loathing by breaking negative thought spirals (analogous to findings in addiction research). A small case series in a review suggested that psychedelics resulted in a reduction in binge-eating/purging episodes in a few BN patients, but these data are anecdotal. MDMA could potentially contribute to the treatment of eating disorders by promoting emotional processing and trust. Many eating disorders (particularly AN and BN) involve underlying emotional avoidance mechanisms; MDMA could reduce fear of change and intimacy, making patients more open towards therapists or loved ones (for example, in sessions involving a family member, as in the MAPS study). This could, for example, help to break through denial or facilitate discussion of traumatic experiences that fuel the eating disorder. But again, this remains hypothetical until the MDMA-AN study yields results. In conclusion, the preliminary data on psilocybin in anorexia suggest a potential therapeutic effect: a reduction in obsessive thoughts related to the eating disorder, reduced anxiety and possibly improved motivation to recover. Actual behaviour (weight normalisation) does not change instantly, but psychedelics may be able to provide a psychological nudge that traditional therapy can then build upon.
4. Risks/Contraindications: In the case of eating disorders, a number of specific risks must be highlighted. First and foremost is medical vulnerability: severe underweight (BMI < ~16), electrolyte imbalances (potassium deficiency due to vomiting), or organ complications (such as liver or kidney failure due to malnutrition) constitute absolute contraindications for MDMA/psilocybin until these have been corrected. A patient with a BMI of 13 and unstable vital signs would be at risk of death if they used MDMA, due to cardiac arrhythmias or seizures. In a controlled study setting, therefore, only relatively stable patients are likely to be included. Secondly, one must take into account the mental rigidity and need for control that characterise anorexia. During a psychedelic session, one temporarily loses control, which may trigger panic or resistance in these patients. Thorough preparation is needed to help them learn to surrender to the experience. Nevertheless, an anorexia patient may become overwhelmed by body image or calorie-related anxiety during the trip. This requires therapists to be very familiar with these issues in order to provide appropriate support. Another risk is that of misinterpreting physical signals: for example, an AN patient may interpret any physical sensation as abnormally intense or negative (somatic introspection is often impaired in AN). During psilocybin use, bodily sensations (hunger, satiety, warmth) may change; the patient might misinterpret this as something threatening. Explaining in advance what to expect is therefore particularly important for this group. MDMA-specific: MDMA carries a risk of dehydration or overheating – anorexia patients sometimes have impaired temperature regulation and do not drink enough. Care must therefore be taken to ensure that, during MDMA sessions, the patient remains hydrated and does not become overstimulated (no intense physical activity, as they are already vulnerable). Blood sugar levels are also a concern: given the observed cases of hypoglycaemia even with psilocybin, it is essential to ensure, as a preventive measure, that patients consume sufficient food around the time of the MDMA session (as MDMA accelerates metabolism). Psychological contraindication: severe comorbid depression with active suicidal ideation is common in eating disorders. Although psilocybin reduces depression in other contexts, care must still be taken to ensure that a person does not enter the session whilst feeling suicidal. This should be carried out in a hospital setting with a crisis plan in place, should suicidal tendencies escalate after the session (although this has not been observed at AN to date). Furthermore, many patients with eating disorders have a history of trauma or family issues; psychedelics can bring these unresolved issues to the surface. Without access to trauma therapy afterwards, this could be harmful. Therefore, integration with, for example, schema therapy, trauma therapy or family counselling afterwards would be essential to process whatever surfaces. In summary: careful patient selection and medical optimisation are crucial. Contraindications include serious physical risks (such as unstable heart function), as well as insufficient motivation or extreme resistance on the part of the patient to this type of treatment. Once these conditions are met, the risks appear manageable and psychedelic therapy offers a promising new approach to treating intractable eating disorders.
Elimination disorders
(Enuresis – bedwetting; encopresis – soiling, etc.)
1. Research: There is no research whatsoever that has explored the use of MDMA or psilocybin in this category of disorders. Elimination disorders occur predominantly in children (bedwetting, soiling), and psychedelics are absolutely not used in young children. Furthermore, these are disorders that are usually treated with behavioural or pharmacological approaches (desmopressin for enuresis) and have a good prognosis; there has been no rationale for using psychedelics in these cases.
2. Safety: Not applicable, given the lack of studies. Furthermore, MDMA or psilocybin would not be administered to children or adolescents except in very exceptional research settings (and elimination disorders rarely occur in isolation even in adults). If we were to consider this theoretically: MDMA and psilocybin have no direct effect on bladder or bowel function, but they can influence consciousness and behaviour – this would likely have a disorientating effect on a child who already has toilet training difficulties. Safety is therefore more of an ethical issue here: these disorders are observed in young people, and it would be unsafe or inappropriate to subject them to such experimental therapy.
3. Therapeutic effect: None. There is no reason to believe that psychedelics would resolve elimination disorders. In children, these problems are often developmentally based or stress-related; the solution lies in behavioural training, psychotherapy targeting underlying stressors, or simply time. In theory, neither MDMA nor psilocybin offers a mechanism that directly resolves problems with wetting or soiling. At most, someone with psychological trauma manifesting as enuresis might benefit from trauma therapy, but that would then fall under the heading of PTSD (and if that person also happens to have enuresis, it might help indirectly). However, specifically, no therapeutic effect is known or has been studied.
4. Risks/Contraindications: The main contraindication here is actually age and developmental stage: it is not responsible to expose such young people (usually under 16) to these substances, except perhaps in a highly experimental setting involving late adolescents. Furthermore, children would find it very difficult to understand and process these substances, which poses a risk to their mental health. Physiologically, MDMA or psilocybin might affect bladder function to some extent – for example, MDMA can increase vasopressin, which promotes water retention, but this is speculative and not relevant to resolving toilet training issues. A potential risk if one were to administer it anyway (say, to an adult with a neurogenic bladder or similar condition) is that control over the sphincter muscles may be reduced during the trip (there are people who, whilst under the influence of ayahuasca or during vomiting, lost sensation in their sphincter muscles and experienced unplanned urination or defecation). In someone who already struggles to maintain control, a hallucinogenic state could temporarily exacerbate this. However, this has not been investigated further. In conclusion: no indication, no research, and therefore no known specific risks apart from its general unsuitability.
Sleep-wake disorders
(E.g. insomnia, narcolepsy, respiratory sleep disorders, circadian rhythm sleep disorders.)
1. Research: Not available. There are no clinical studies evaluating MDMA or psilocybin as a treatment for primary sleep disorders. It is, however, known that psychedelics affect sleep architecture (psilocybin can influence REM sleep parameters on the night following ingestion, whilst MDMA is stimulating and may cause insomnia on the first night). These effects are, however, side effects, not therapeutic properties. Experiments have been conducted with microdosing LSD or psilocybin to investigate whether this can improve daytime alertness (in cases of hypersomnia) or mood in patients with sleep apnoea, but none of this has been rigorously demonstrated in published research. Sleep disorders are generally the domain of behavioural interventions and conventional medication; psychedelics do not form part of this.
2. Safety: On the contrary – MDMA is known to have an adverse effect on sleep when used acutely: it temporarily suppresses the need for sleep (hence all-night dancing at parties) and subsequently disrupts the sleep cycle. Taking MDMA in the evening almost always leads to insomnia that night and often to restless sleep in the nights that follow. In people with sleep disorders (such as insomnia), MDMA could acutely exacerbate the problem. Psilocybin is less stimulating but, due to the intense experience, may also temporarily affect sleep (many patients sleep more lightly or experience vivid dreams the night after their session). In a research context, this is not a major problem as participants are warned about it. However, from a safety perspective, there is no research indicating that it is inherently unsafe for patients with sleep disorders – rather, the evidence is inconclusive. However, someone with, for example, narcolepsy who already has abnormal neurotransmitter levels could react unpredictably to psychedelics (no data available, but caution is advised). In general terms, the standard safety criteria apply; sleep disorders in themselves are not a somatic contraindication. It is simply that the timing of dosing must be right (obviously, psychedelics are not administered just before bedtime).
3. Therapeutic effect: No direct effect is known. Theoretically: if a sleep disorder is secondary to trauma or depression, treating that underlying condition with MDMA/psilocybin could improve sleep quality. For example, PTSD patients often experience nightmares; in the MDMA-PTSD trials, it was reported that nightmares and sleep showed improvement in parallel with a reduction in PTSD symptoms. Thus, indirectly, sleep may benefit from successful psychedelic therapy for comorbid disorders. However, for primary insomnia, there is no evidence that psychedelics improve sleep latency or sleep efficiency. In fact, psilocybin may cause more intense dreams during the first few nights (some report vivid, sometimes disturbing dreams as an after-effect, whilst others find them insightful). This might even be unpleasant for someone with a nightmare disorder. In short, there is no evidence of a therapeutic effect on sleep disorders.
4. Risks/Contraindications: There are few risks specific to sleep disorders, apart from the fact that psychedelics can acutely disrupt the sleep cycle. For someone with severe insomnia, a sleepless night caused by MDMA may lead to even greater cognitive and emotional disruption the following day. Patients with narcolepsy or REM sleep behaviour disorder could, in theory, experience uncontrolled sleep attacks or motor activity during the trip; this has not been studied, but caution is advised. In general, sleep deprivation is a known trigger for mania and epilepsy – as MDMA can cause sleep deprivation, this could pose an indirect risk to susceptible individuals (who, incidentally, would already be excluded due to bipolar disorder or epilepsy). Contraindications are the usual ones; sleep disorders in themselves are not an exclusion criterion, but they are often associated with other conditions that may constitute contraindications (e.g. sleep apnoea with severe cardiovascular disease, which is a medical concern for MDMA). Many patients with sleep disorders also use sedatives; these must be discontinued prior to psychedelic therapy, which can be difficult. A practical point: if someone is taking strong benzodiazepines as a sleep aid, this could dampen the psychedelic experience or require them to stop taking them beforehand – which may lead to rebound insomnia. However, this is manageable under supervision. In summary: sleep-wake disorders are not a direct target for psychedelics, and therefore present few specific risks or contraindications beyond the general principles.
Sexual dysfunctions
(E.g. erectile dysfunction, arousal disorder, problems reaching orgasm, vaginismus.)
1. Research: There is no research available that directly examines MDMA or psilocybin as a treatment for primary sexual dysfunctions. In the 1980s, however, MDMA became informally recognised as a ‘therapeutic aid“ in couples” therapy – it was thought to promote emotional openness between partners. But this did not relate to a specific sexual dysfunction, but rather to general relationship improvement. For example, no randomised study has administered psilocybin to see if it alleviates vaginismus, or MDMA to treat premature ejaculation. These applications have not been investigated in clinical trials. That does not mean there is no connection whatsoever: there are anecdotal accounts of people who say that a psychedelic experience helped them with body acceptance or confidence, which indirectly improved sexual function. But hard scientific data is completely lacking.
2. Safety: In the context of sexual dysfunction, safety is more of a pharmacological issue: MDMA and psilocybin are not inherently dangerous to the genitals or similar areas, so they do not pose any particular physical problem. However, it is important to realise that MDMA has certain acute sexual effects: the drug can increase desire and sensuality when taken (people often feel more connected and tactile), but, paradoxically, MDMA often causes erectile dysfunction or delayed ejaculation whilst under the influence, due to strong serotonergic activation. This is a well-known phenomenon amongst recreational users (“love drug” in terms of emotion, but physically it can sometimes make sex difficult). Psilocybin has a less clear-cut effect on sexuality – high doses usually lead to such an altered state of consciousness that sexual arousal is not the primary focus, though there are also reports of increased sensitivity. In terms of safety: there is no reason to assume that someone with a sexual dysfunction would be unable to tolerate MDMA/psilocybin; the usual criteria apply. Possibly relevant: some men with erectile dysfunction use nitrates as medication; MDMA combined with nitrates can be dangerous (drop in blood pressure). However, this is a remote possibility unless one were actually to consider this as a form of therapy for someone using, for example, poppers or nitroglycerine (which, of course, would not be done). In conclusion: there are no unique safety concerns, apart from the fact that these substances must certainly not be taken alongside drugs such as Viagra or poppers due to cardiovascular interactions – but in a therapeutic context, this combination would not normally occur.
3. Therapeutic effect: There is no proven direct effect of MDMA or psilocybin on, for example, the long-term restoration of erections or libido. However, it could be argued that if sexual dysfunction has a psychogenic cause (e.g. performance anxiety, trauma, lack of a sense of intimacy), psychedelic therapy could indirectly bring about an improvement in this area. For example: someone with vaginismus caused by past sexual trauma might, through MDMA therapy, process that trauma and subsequently experience less pain and greater relaxation during sex. To that extent, MDMA or psilocybin could have a positive effect on sexual function through psychological healing. From PTSD studies, we know that women with sexual trauma report less sexual avoidance and greater satisfaction following successful MDMA therapy (secondary outcomes, not formally published but anecdotal). However, this has not been quantitatively established specifically as an outcome measure. Psilocybin can induce strong feelings of oneness and acceptance of one’s own body; this could potentially help people with sexual inhibitions or body image issues (which get in the way of sex). But again, this is theoretical. In fact, sexual dysfunction often falls within the medical or relational domain (urology, gynaecology, relationship therapy). Psychedelics are not currently regarded as an intervention in these areas. MDMA is perhaps the most plausible option in the context of sex therapy, as it promotes empathy and open communication – there are reports that couples in the 1980s used MDMA to improve their relationship and, consequently, their sex life. However, this does not yet constitute a clinical guideline. In summary: for the time being, there is no empirically demonstrated therapeutic benefit of MDMA or psilocybin for sexual dysfunction, at most an indirect benefit via the improvement of underlying psychological factors.
4. Risks/Contraindications: A practical risk is that, if someone uses MDMA in an uncontrolled manner to enhance sexual experiences, it may lead to unsafe behaviour. For example, it reduces anxiety so significantly that people may forget to use condoms or respect boundaries (this is more relevant in recreational settings than in therapy where a professional is present). In a therapeutic setting, this risk is minimal, as no sexual interaction takes place during sessions – on the contrary, therapists maintain a professional distance. Contraindications are therefore again general in nature: if someone also has a cardiovascular condition that already limits their sexual activity, then MDMA is also dangerous. Or if the sexual dysfunction is part of another disorder (e.g. anorgasmia caused by SSRI use), it must first be assessed whether that context can be altered (SSRIs must be tapered off before psychedelic therapy anyway, which may already improve sexual function). Another potential risk is disappointment or frustration: suppose someone with erectile dysfunction takes psilocybin in the hope of a “cure” and this does not happen immediately – that person may become disappointed or blame themselves. Good information and a realistic framework are therefore essential. Furthermore, we must recognise that some sexual dysfunctions have a strong somatic component (e.g. nerve damage in diabetes, or vascular problems) – psychedelics will, of course, not resolve these. A risk here would be that people might delay or reject valuable medical treatment in favour of an ineffective psychedelic intervention. This is more of an ethical concern than a direct health risk posed by the substance. In short, there are no specific contraindications for psychedelics in this group apart from the general ones, as there is no evidence-based indication for using them at all. If used, one must simply be wary of misuse (for example, MDMA in a sexual context can lead to dehydration if one is physically active for hours on end – this is a well-known recreational risk, but in a therapeutic setting one would not allow that to happen). All in all: not recommended outside of research, so these risk considerations are largely hypothetical.
Gender dysphoria
1. Research: None. There are no scientific studies on MDMA or psilocybin specifically for the treatment or management of gender dysphoria. Gender dysphoria (GD) is not a “mental disorder” in the traditional sense, but rather a sense of discomfort with one’s assigned sex, and treatment often involves hormonal therapy and psychotherapeutic support aimed at a potential transition. Psychedelics have not yet come to the fore in this field. It is possible that individuals with GD may have used psychedelics in a personal context to better understand themselves, but this has not been documented in the literature.
2. Safety: In principle, there would be no immediate medical reason why someone with gender dysphoria could not tolerate MDMA or psilocybin – the substances are safe provided the general criteria are met (no serious heart problems, no psychosis, etc.) – regardless of a person’s gender identity. However, this is a vulnerable population: trans people have, on average, higher rates of depression, trauma and suicidal ideation. So safety here is primarily about mental health support. Without research, it’s anyone’s guess, but it’s fair to say that psychedelics can be safe provided there is appropriate support and screening – just as with other populations.
3. Therapeutic effect: There is no evidence that MDMA or psilocybin reduce gender dysphoria. Gender dysphoria relates to a mismatch between gender identity and the body; standard care involves transitional support (hormones/surgery) and psychological support. A psychedelic experience might potentially help someone to accept themselves or provide creative insights into their identity. Anecdotally, some transgender people report that psychedelic experiences increased their sense of unity with their body or their sense of acceptance. MDMA might conceivably temporarily reduce anxiety and shame surrounding one’s own body, which could be useful in therapy when discussing self-image. However, all of this is speculative; there are no studies, so there is no proven therapeutic effect.
4. Risks/Contraindications: Comorbid conditions are the main area of concern here. Many people with gender dysphoria have experienced trauma (e.g. bullying, discrimination) or depression. The risks of MDMA/psilocybin in this context have already been discussed elsewhere (see the PTSD/depression sections). Great care should be taken not to raise false expectations, as if a trip could “cure” someone’s gender dysphoria. This could, in fact, lead to disappointment and further distress if the dysphoria persists. Other contraindications are the usual ones – gender dysphoria in itself is not a contraindication, but if someone is, for example, undergoing hormone therapy, it must be assessed whether this is medically compatible (in principle, it is; as far as is known, the use of oestrogen or androgens does not directly interfere with psychedelics). A potential risk: if psychedelic therapy is administered inappropriately, it may also increase confusion in someone who is already struggling with their identity. For example, an intense vision could temporarily confuse someone about their own identity – without proper integration, this could be detrimental. In professional hands, this should be managed. In general: there is no specific contraindication, but there is little rationale and it is potentially risky speculation to present psychedelics as a solution for gender dysphoria.
Disruptive, impulse control and behavioural disorders
(E.g. oppositional defiant disorder (ODD), conduct disorder (CD), intermittent explosive disorder.)
1. Research: There are no known clinical trials that use MDMA or psilocybin to treat these disorders. These diagnoses are common in children or adolescents (ODD, CD) or are associated with forensic populations (antisocial behaviour). To date, psychedelics have not been investigated as an intervention for behavioural problems or impulse control disorders in these groups. In adults, one might consider conditions such as intermittent explosive disorder – yet again, there is nothing in the literature regarding the use of MDMA or psilocybin for this condition. Some symptoms may overlap with PTSD or personality disorders, where research into related behaviour has been conducted (for example, aggression decreased in some PTSD treatments as part of an improvement in PTSD symptoms). However, there is a lack of direct research within this DSM-5 category.
2. Safety: As this primarily concerns young people and often less motivated groups (sometimes in a coercive context), safety is more a matter of the setting. Psychedelics require the individual to cooperate and be in a safe environment – someone with a severe behavioural disorder could react unpredictably or become aggressive whilst on a trip, which could be dangerous for those supervising them. There is no pharmacological contraindication – MDMA and psilocybin would have the same physical effect – but behaviour whilst under the influence can be problematic. Someone with impulse control problems might impulsively do something foolish during a session (e.g. running away, smashing a window whilst in a confused state). For this reason, from a safety perspective, it is very important that the environment is controlled. In a research context, this is feasible (a quiet room and several therapists can be provided). However, once again, without studies we cannot be certain. In theory, MDMA has empathogenic effects that can dampen aggression (people often become gentle and affectionate on MDMA), so perhaps it is safe in the short term because it actually promotes prosocial behaviour. There is some evidence that psychedelics (psilocybin, LSD) have a long-term anti-aggressive effect – in population studies, for example, psychedelic use has been associated with lower levels of intimate partner violence. This suggests that, if there is an effect, it is more likely to reduce aggression. However, pending hard data, this remains speculative and safety has not really been tested.
3. Therapeutic effect: Not demonstrated. One might argue that if an impulse control disorder (such as explosive anger) stems from underlying trauma or emotional dysregulation, MDMA or psilocybin therapy could help by facilitating insight and processing. For example, an adult with intermittent explosive disorder who is actually dealing with unresolved trauma might, through MDMA, be able to delve deeper into the feelings underlying the anger and learn to cope with them differently. MDMA promotes emotional recognition and empathy, which could help to reduce aggressive or antisocial behaviour. For example, there is a hypothetical article suggesting that MDMA might help with antisocial personality traits through its pro-social effects, but there is no actual data to support this. Psilocybin temporarily increases the personality dimension of openness, which may reduce rigidity and black-and-white thinking – for someone with ODD (who can often be rigidly rebellious), this might create scope for behavioural change. However, this is merely a theory; there is no experimental confirmation. To date, there is no proven therapeutic effect of psychedelics on disorders such as ODD/CD. It is interesting to note, however, that psychedelics are linked to improved empathy and moral judgement; for example, there are correlational studies associating lower levels of criminality with a history of psychedelic use, but this is not hard evidence of causality or treatment potential.
4. Risks/Contraindications: The greatest risk is that individuals with these disorders (particularly CD and antisocial traits) may not respect the setting or may misuse the experience. Independent use of psychedelics by people with impulse control and behavioural problems is dangerous, as they may be prone to reckless behaviour (for example, driving under the influence or overstepping boundaries). In a therapeutic context, supervision is required to prevent them from harming themselves or others during the session. Contraindications are, once again, the usual ones: a history of violent behaviour combined with psychedelic use is not an automatic exclusion criterion, but extra security measures should be considered. Another risk: in young people with CD/ODD, the personality is still developing; some believe that the use of such potent substances at a young age may be detrimental to mental health. This is why such experiments are not carried out on minors. In adults with antisocial tendencies – who may also often have subtle neurological abnormalities – it is not known how they will react; there could be a risk of an unpredictable response, such as paranoia, or, conversely, no effect at all if they try to shut themselves off emotionally. Regarding contraindications: if a person’s behavioural disorder is accompanied by substance abuse (which is common in CD), this must also be taken into account – active addiction is a contraindication unless it is the addiction itself that is being treated (see the section on addiction). In summary: whilst there may be potential societal benefits if aggression and impulsivity are reduced, the risk is high if this is applied to uncooperative or unstable individuals. That is why it is not practised outside of hypothetical discussions. At present, psychedelics should not be used to treat disruptive behavioural disorders, except perhaps in future research involving extremely careful patient selection.
Substance-related and addictive disorders
(Addiction disorders caused by alcohol, nicotine, opioids, stimulants, etc., including substance use disorders and gambling disorders.)
1. Research: This is an area where psychedelics are actually showing surprisingly strong results. Psilocybin has been extensively studied in relation to addictions, particularly tobacco and alcohol addiction. In an open-label pilot study (Johns Hopkins University), 15 adults dependent on nicotine received psilocybin-assisted therapy (three sessions) to support their efforts to quit smoking. The outcome was remarkable: after 6 months, 80% of the participants were still abstinent from smoking, as verified by biological tests. After 12 months, 67% were still smoke-free, and at long-term follow-up (~2.5 years), ~60% were still maintaining abstinence. These abstinence rates (67–80%) are much higher than those achieved with conventional cessation methods (where a success rate of ~30% at 6–12 months is already considered good). Psilocybin was subsequently tested in a randomised controlled trial for alcohol use disorder (AUD): in 2022, Bogenschutz et al. published an RCT involving 95 alcohol-dependent patients, comparing psilocybin sessions (2 × 25–40 mg per 70 kg) with an active placebo (diphenhydramine) plus psychotherapy. Results: over a 32-week period, psilocybin patients had significantly fewer heavy drinking days than the placebo group – on average ~9.7% heavy drinking days versus ~23.6% in the placebo group. This means that the psilocybin group remained abstinent or drank moderately much more frequently; specifically, the psilocybin group drank excessively on ~1 in 10 days, compared with ~1 in 4 days in the placebo group. Furthermore, a larger proportion of the psilocybin group achieved complete abstinence: by the end of the trial, ~48% of the psilocybin group had become completely abstinent, compared with ~24% of the placebo group (figures from JAMA Psychiatry 2022). These differences were statistically significant and clinically relevant. The total number of days of consumption also decreased, and the effect persisted during the follow-up. In summary: psilocybin-assisted therapy had a major effect on reducing alcohol consumption among addicts who were motivated to do so. In addition, studies into psilocybin for other substances are currently underway or have been conducted: e.g. cocaine addiction (University of Alabama pilot, still ongoing), opioid addiction (preclinical interest, limited human data to date) and cannabis use disorder (a small RCT has been set up for treatment-resistant cannabis-dependent individuals; results not yet known). A relatively new area of focus is psilocybin for behavioural addictions (such as gambling); no results are available yet, but conceptually it could be effective (reflected, for example, in improved cognitive flexibility). MDMA has been studied less extensively in the context of addiction, but is gaining ground. A groundbreaking open-label study in 2019–2020 (Bristol Imperial MDMA in Alcoholism, BIMA) tested MDMA-assisted psychotherapy for alcohol dependence (14 patients). The MDMA sessions were designed to facilitate emotional breakthroughs and boost motivation following detox. Results: the MDMA therapy was safe and well-tolerated (see Safety), and the outcomes showed a significant reduction in alcohol consumption. On average, 9 months after treatment, patients were consuming only ~18 units of alcohol per week, compared with ~130 units per week before detox and therapy. This represents a dramatic reduction in consumption. A large proportion of the group remained completely abstinent; others experienced lapses but no full-blown relapse. Although this was not an RCT, the findings are very encouraging. They suggest that MDMA therapy can significantly improve relapse prevention in AUD. A larger controlled study is now being conducted to validate these findings. Furthermore, MDMA has recently been investigated in a comorbid population: patients with both PTSD and alcohol dependence (as these conditions often co-occur). Here, too, it was found that MDMA therapy not only improved PTSD symptoms but also significantly reduced eating disorder symptoms compared with placebo. This suggests that even if MDMA works indirectly through trauma healing, addictive behaviour may also decrease. Finally, there are small case reports or trials involving other classic psychedelics in the context of addiction: for example, ketamine (not a classic psychedelic but a dissociative) has been studied in relation to alcohol and opiates with positive results, and ibogaine (a non-oneirogenic substance) has been studied for opioid addiction – but this falls outside the scope of MDMA/psilocybin. For stimulant addiction (cocaine, amphetamines), psilocybin is still at the exploratory stage – no firm conclusions have been drawn, although there are plans in place. In conclusion: yes, there is substantial research showing that psilocybin (and, increasingly, MDMA) can be used safely and potentially effectively in the treatment of substance use disorders, particularly tobacco and alcohol, but there is also promise for other substances.
2. Safety: In the context of addiction treatment, safety has two aspects: the pharmacological safety of the drug itself and its effect on addictive behaviour (i.e. not triggering a new addiction). The results are favourable in both respects. Pharmacological: Patients with addiction are sometimes in poorer physical health (e.g. liver damage in alcoholics, cardiovascular disease in smokers). Nevertheless, the studies show that psilocybin is well tolerated in these populations. In the smoking cessation study and the alcohol study, no serious side effects were reported from psilocybin; headache was the most common complaint reported afterwards. In the alcohol RCT, 77% of the participants experienced some mild side effects (headache, nausea, dizziness), evenly distributed across the psilocybin and placebo groups. There were no differences in suicidal ideation or serious psychiatric events between the groups – an important finding, as one might expect psychedelics to exacerbate cravings or depression, but this did not occur. MDMA for addiction (the BIMA study) also proved to be well tolerated: all 14 participants underwent two MDMA sessions without any unexpected problems. There were no unexpected adverse events; everyone completed the treatment. Psychosocial functioning actually improved across the board in that group. This suggests that even vulnerable clients (who had recently undergone alcohol detoxification) were able to cope with MDMA both physically and mentally. Naturally, medical criteria were applied (stable following detox, no longer experiencing acute withdrawal symptoms, normal laboratory values). Safety does, however, require that the patient be free of the addictive substance at the time of the session – this is crucial. In all studies, for example, a detox or period of abstinence was first completed before administration. This is particularly necessary with alcohol, otherwise there is a risk of interactions (alcohol plus MDMA = risk of dehydration/overheating) and unpredictability. With nicotine, this is less of an issue (patients smoked right up until just before taking psilocybin, which was not a problem; some even smoked during integration sessions). Nevertheless, no cases of acute nicotine poisoning or similar were observed. A major safety consideration is avoiding serotonergic medication: many addicts take antidepressants; these must be discontinued before taking psilocybin or MDMA (we repeat this often because it is essential). This was properly managed in the studies and is apparently feasible under supervision. The second safety consideration is addictive behaviour itself: could someone become addicted to psilocybin or MDMA? The studies and follow-up suggest not. On the contrary, there are no reports of participants subsequently abusing MDMA or psilocybin – even in the follow-ups, no signs of increased recreational use or drug-seeking behaviour towards the substance under investigation were observed. For example, in the MDMA-PTSD alcohol study, researchers continued to monitor whether anyone was taking MDMA outside the sessions; this did not happen. Psilocybin is known not to be addictive (no physical dependence and rarely an urge to repeat use frequently due to an intense trip). MDMA does have the potential for recreational misuse, but this has not been observed in a therapeutic context. Patients viewed it as part of their therapy and did not experiment with it at home (particularly as they had signed a contract undertaking not to do so during the study). Conclusion on safety: Both psilocybin and MDMA can be used safely with addicts in remission, provided there is proper medical supervision and sobriety during sessions. There is no evidence that these substances cause new addiction; rather the opposite – they break the cycle of addiction.
3. Therapeutic effect: The results are nothing short of promising. Tobacco addiction: psilocybin therapy showed an exceptionally high quit rate (80% at 6 months). By way of comparison: conventional stop-smoking methods (patches, varenicline) have a success rate of around 25–35% at 6 months. This difference illustrates the potential: psilocybin sessions combined with motivational therapy led to what the researchers described as “unprecedentedly high abstinence rates”. The majority of smokers described the psilocybin experience as one of the most meaningful of their lives, fundamentally changing their perspective on smoking. They felt as though they had wrested themselves “from the grip” of nicotine and developed an aversion to, or lack of desire for, cigarettes. This effect was found to largely persist in the long term among those who had initially quit. Alcohol addiction: Here, too, we see that psilocybin therapy had a powerful effect: a halving of the number of days of heavy drinking compared with the placebo group. Furthermore, the psilocybin group had significantly more days of complete abstinence (the average number of drinking days per week was lower). Specifically: patients who underwent two psilocybin sessions were much less likely to relapse into their old drinking patterns during the eight-month follow-up than those given a placebo. Here too, many reported that the session gave them deep insight into why they drank, sometimes accompanied by a confrontation with repressed emotions or a motivation to live a better life. Some patients described the experience as “the moment when I forgave myself and was able to let go of the bottle”. The accompanying psychotherapy (motivation enhancement and CBT) was clearly enhanced by the psilocybin: the psilo group had stronger therapeutic alliances and greater cognitive flexibility to embrace new coping skills, according to qualitative analyses. MDMA for alcohol: The open-label results showed that MDMA-assisted therapy following detoxification had a highly beneficial effect on relapse prevention. On average, participants remained close to abstinence, and anecdotally, ~85% were still completely alcohol-free after 9 months (the BIMA study reported that 11 out of 14 participants had not experienced a single full relapse during that period) – which is unprecedented among heavy drinkers. The mechanism is that, during the therapy sessions, MDMA helped them process underlying traumas or emotions that underpinned their drinking behaviour, whilst also increasing self-love and connection, thereby reducing the need to numb themselves. Furthermore, improvements were observed in quality of life and resilience. Studies combining MDMA and PTSD treatment also show that addictive behaviour improves when trauma is treated: patients with PTSD and substance misuse saw both their PTSD symptoms and substance use decrease in the MDMA group compared with the placebo group. Other substances: Although concrete figures are lacking, there is a logical expectation (supported by animal studies and mechanistic insights) that psychedelics can “reset” or at least temporarily loosen craving circuits in the brain. Some small studies with ketamine (a different class but with similar principles of neuroplasticity) also showed increased abstinence rates for alcohol and heroin. Psilocybin and MDMA could, through deeper spiritual and motivational insights on the one hand and socio-emotional healing on the other, help addicts achieve a breakthrough where conventional treatment fails.
To summarise in concrete terms: psilocybin therapy resulted in high smoking cessation rates and a clear reduction in alcohol misuse, with effect sizes that are substantial. Preliminary data suggest that MDMA therapy has shown almost comparable success with alcohol, with many participants remaining abstinent over the long term. Both substances therefore appear to be potentially effective in treating addiction, albeit via slightly different mechanisms. Psilocybin is often associated with transcendent or existential insights that help an addict give their life new meaning (thereby weakening the grip of addiction). MDMA is associated with the restoration of damaged emotional processes, which can, for example, break the cycle of trauma-related addiction. For most addictions, comorbid PTSD or depression is common; these can be treated simultaneously (MDMA is particularly effective for PTSD, whilst psilocybin is effective for depression). The ultimate effect is that patients report a significant reduction in cravings, that they have experienced “a reset” or now view the substance differently – often with a greater sense of self-efficacy to say no. This is also reflected quantitatively in a drastic reduction in hours/days of use and higher abstinence rates than usual.
4. Risks/Contraindications: There are a number of specific points to bear in mind with patients suffering from addiction. Prior detoxification or stabilisation is essential: anyone still under the influence of alcohol or benzodiazepines must under no circumstances undergo a psychedelic session – not only because of potential interactions (alcohol plus MDMA can cause dehydration and overheating; benzodiazepines inhibit the effects of psilocybin) but also because the session will not be effective cognitively or emotionally. Abruptly stopping certain addictive substances can be dangerous in itself (withdrawal from alcohol or benzodiazepines can cause seizures or delirium), so this process must be medically supervised before starting with MDMA or psilocybin. This has always been the case in research. The acute risk during the session is low provided the person is sober, but suppose someone has secretly taken something: for example, cocaine in the system combined with MDMA can exacerbate heart problems – this is a scenario for which strict testing is carried out (urine drug screening, etc.). One risk, therefore, is patient non-compliance: people with substance use disorders may be inclined to lie about their use. Strict monitoring and trust are essential. Participants must also be sufficiently motivated psychologically; court-ordered scenarios (compulsory) would not work well, as psychedelics require openness on the part of the participant. Contraindications overlap with those already mentioned: a history of schizophrenia or bipolar psychosis is a contraindication (including among drug addicts, as they are also affected). Many addicts have cardiac damage (e.g. stimulants have affected their heart, or alcohol has raised their blood pressure), so a full medical check-up is required to determine whether their body can cope with the session. Severe liver cirrhosis, for example, can impair metabolism; MDMA is metabolised in the liver, so in cases of severe liver failure, titrating the MDMA dose would be difficult (and there is a risk of accumulation). This must be assessed on a case-by-case basis. Interaction with addiction treatment medication: If someone is on opioid agonists (methadone, buprenorphine) – little is known about how these interact with psilocybin. Theoretically, it does not directly inhibit the trip, but high doses of methadone can cause QT prolongation; in combination with MDMA (which can also prolong the QT interval), this is potentially dangerous. This must therefore be monitored (ECG). In a nicotine study, participants smoked right up until just before and after taking psilocybin – this did not result in any incidents, but smoking increases adrenaline, which could have contributed to a hypertensive reaction; however, this was not observed nor did anyone experience any problems as a result. Avoiding the development of new addictions: Although no misuse of psychedelics has been observed in research, it is important to emphasise outside the research context that psychedelic therapy does not mean the patient is free to experiment on their own at home. It is safe in a controlled setting, but if a former addict thinks, “Those magic mushrooms help me, so I’ll take them every week now”, this could lead to psychological destabilisation. Fortunately, psilocybin and MDMA are not physically addictive, but psychologically, anything can be misused. Therapists must therefore provide thorough psychoeducation to make it clear that this is not self-medication and that frequent use is counterproductive (due to tolerance, the need for integration, etc.).
Another risk: environmental triggers. In the case of alcoholics, for example – if, after therapy, they return to a dysfunctional environment full of friends who drink, there is a risk of relapse (albeit possibly a lower one). Psychedelic therapy does not confer magical immunity; aftercare and structural lifestyle changes remain crucial. This is not a direct risk posed by the substance itself, but rather by the treatment process: overestimating the substance’s effectiveness can lead to inadequate aftercare, and consequently to relapse.
Finally, suicidal tendencies are a cause for concern, as many people with addictions experience them. So far, the data show that suicidal ideation does not worsen – this was not an issue among smokers, whilst alcoholics were actively monitored and no difference was found between groups. Nevertheless, suicidal tendencies must be closely monitored; someone who gives up their substance of choice (e.g. alcohol) may temporarily experience raw emotions. Fortunately, the psychedelic session often provides sufficient emotional processing, but it remains important to pay attention to this during the integration phase.
Summary of contraindications: Inadequate detoxification, severe physical complications of addiction (heart failure, liver failure, uncontrolled epilepsy caused by alcohol), severe psychiatric comorbidity (schizophrenia, bipolar I disorder) – these exclude participants. Once these have been ruled out, MDMA and psilocybin appear to be relatively safe and highly promising for this target group, with the benefits outweighing the risks, as current data show.
Neurocognitive disorders
(For example, dementia syndromes such as Alzheimer’s disease, vascular dementia, frontotemporal dementia, or mild neurocognitive disorders.)
1. Research: This is an emerging but still largely theoretical field. To date, very little clinical research has been published on MDMA or psilocybin as a treatment for cognitive impairment or dementia. However, we are seeing some initiatives: for example, a pilot study is currently underway to investigate whether psilocybin can help with depression and quality of life in people with mild cognitive impairment or early-stage Alzheimer’s. This study (at Johns Hopkins and other sites) has begun, but results are not yet available. The rationale behind this is that many Alzheimer’s patients become depressed as a result of their diagnosis, and psilocybin could alleviate that depression and possibly have a direct neurological effect (more on this later). Furthermore, preclinical research suggests that psychedelics have neuroplastic and anti-inflammatory effects in the brain. In animal models, for example, it has been shown that microdosing with psilocybin can promote synaptogenesis in the hippocampus – which is relevant to Alzheimer’s. An uncontrolled, open-label study (2018) involving 33 older adults who had been microdosing for a long time reported improvements in creativity and cognitive flexibility, but these data are limited and may be biased (self-selection). MDMA has not really been studied in this context; in theory, it could reduce social apathy in frontotemporal dementia through a prosocial effect, but this is speculative. In summary: research is still at a theoretical and very early clinical stage. There are as yet no published RCTs or noteworthy case series on actual improvements in cognitive scores due to psychedelics in dementia.
2. Safety: Older patients with neurocognitive disorders often have multiple medical conditions – this makes safety a key concern. There are as yet no large-scale studies, so we must draw conclusions from smaller studies involving older adults. A psilocybin study on depression (in which some participants were aged between 55 and 65) found no age-specific increase in adverse effects; older participants tolerated psilocybin in much the same way as younger ones, although they did experience slightly more occasional headaches or high blood pressure. However, people with dementia may be more vulnerable: they often have cardiovascular risk factors, which means that, for example, MDMA (which increases heart rate and blood pressure) is riskier. They also frequently take multiple medications (beta-blockers, anticoagulants, cholinesterase inhibitors) – potential interactions are unknown. Cognitive safety is crucial: someone with dementia already has problems with orientation; a psychedelic experience can acutely increase their confusion. There is a risk of delirium during or after the session if things do not go well. This is a real risk, as older people are more susceptible to episodes of delirium when their equilibrium is disrupted. This should therefore only be attempted in a hospital setting. MDMA in older people: MDMA places a strain on the cardiovascular system (peak heart rate and vasoconstriction) and may be riskier in older people due to reduced temperature regulation. No studies exist, but caution is advised. Psilocybin is physiologically milder, but even so – if someone is severely forgetful, panic and disorientation may occur (which does cause blood pressure to rise again). In summary, safety remains unclear: there is no evidence to suggest it is unsafe, but extreme caution is required. The ongoing pilot studies are likely to include only mild cases (who are able to give informed consent and are reasonably fit). Furthermore, there are ethical considerations: people with advanced dementia cannot give informed consent, so research would be limited to the mild stage.
3. Therapeutic effect: Unknown in terms of cognitive enhancement. There are hypotheses that psychedelics might influence the pathological processes of Alzheimer’s disease. For example, that by stimulating the 5-HT2A receptor, they promote neurogenesis and synaptic repair in the hippocampus and cortex. They are also thought to modulate brain network connectivity – which could be beneficial if certain networks (such as the default mode network, etc.) are overactive or underactive in dementia. However, this is theoretical; in practice, Alzheimer’s is a degenerative disease characterised by amyloid/tau pathology that cannot simply be halted by neuroplasticity. Psychedelics are therefore unlikely to be a cure, but could provide symptom relief: for example, alleviating depression and existential anxiety caused by dementia, just as has been observed in cancer patients. An improvement in mood and anxiety may indirectly enhance cognitive functioning, as the person shows greater engagement and participates more effectively in rehabilitation. It has also been suggested that microdosing LSD or psilocybin may increase cognitive flexibility – potentially useful in early-stage dementia to help maintain functioning for longer. A mini-review notes that, anecdotally, microdosers report improved concentration and problem-solving skills, which would be welcome in Alzheimer’s disease, but rigorous trials have not been conducted. MDMA could theoretically help with the apathy often seen in dementia – perhaps leading to more interaction through its prosocial effects; it might also help with emotional lability (some frontotemporal patients are anxious or aggressive; MDMA can make them calmer and more empathetic). But that is still pure theory; there are no studies to back it up. Specifically: from a clinical perspective, the ongoing study into psilocybin for MCI is examining whether depression scores and quality of life improve – not even primarily whether cognition itself improves (although they may measure this as a secondary outcome). This in itself suggests that the therapeutic benefits are expected to lie more in mental wellbeing than in core cognitive abilities. A valuable effect would be, for example, if someone with early-stage Alzheimer’s were less anxious about their future, or became more sociable in the time they have left, or accepted more readily that they need help – these are psychosocial benefits.
4. Risks/Contraindications: In the case of neurocognitive disorders, there are a few clear contraindications: advanced dementia (if a person does not understand the protocol or is unable to describe what they are experiencing, this is ethically and practically problematic) – such individuals should not be included. A tendency towards psychosis or delirium, for example in the context of Lewy body dementia, is also a contraindication, as psychedelics would exacerbate these conditions. Patients with Lewy body dementia already experience hallucinations; psilocybin would cause chaos. Furthermore, it should not be forgotten that most older people in this category are taking medication: cholinesterase inhibitors, memantine, sometimes antipsychotics, antidepressants – many of these must be tapered off or temporarily discontinued, which is risky in itself (stopping an antipsychotic can worsen behaviour, whilst stopping an SSRI can cause withdrawal symptoms). This makes it risky to even reach the trial phase. Physical contraindications would include: severe cardiovascular disease (which is almost always excluded from psychedelic studies, but is particularly relevant in the dementia population as vascular disease is often a contributing factor). A specific risk is the exacerbation of disorientation: a person with a cognitive disorder might, following a psychedelic session, temporarily exhibit even more severe cognitive impairment (acute delirium). In a fragile brain, this could potentially lead to residual deterioration. Although this is unlikely (cognitive functions normally recover once the effects have worn off), one cannot be certain in the case of a pathologically affected brain. It is something that will be closely monitored – if a subject remains in a confused state for longer than usual after the session, this is problematic. Emotional effects: just as with others, a psychedelic trip can evoke difficult emotions; in people with dementia, for example, it could bring to the surface a confrontation with their own decline or mortality. This can be beneficial (as with cancer patients) or frightening. Integration is crucial here, and informal carers may need to be involved to help make sense of the experience. With MDMA, there is a risk that it may raise body temperature; older people have poorer temperature regulation, which can lead to hyperthermia or, conversely, a sudden drop in temperature afterwards if they do not drink or cool down in time – so close monitoring is essential.
Generally speaking, neurocognitive disorders remain a grey area for psychedelics. Contraindications would include cases where the disorder is too advanced or is accompanied by other significant problems (psychosis, physical frailty). If they are to be used at all, it would likely be in mild cases involving otherwise relatively healthy, well-supervised patients. The risks would then, hopefully, be manageable. Finally, even though this is not a direct risk associated with the substance, extra attention must be paid to mental capacity and informed consent in this population. For example, if someone has a poor memory, care must be taken to ensure that they are properly informed each time (reminded of what is going to happen), otherwise anxiety and confusion may increase.
In conclusion: there is still much we do not know. At present, the use of MDMA/psilocybin in the treatment of dementia should be restricted to research settings and carried out with the utmost care, given the medical and ethical complexities involved.
Persoonlijkheidsstoornissen
(Bijv. borderline persoonlijkheidsstoornis, vermijdende, antisociale, etc.)
1. Onderzoek: Formeel klinisch onderzoek is minimaal tot afwezig. Traditioneel werden mensen met ernstige persoonlijkheidsstoornissen uitgesloten van psychedelica-onderzoek (bijvoorbeeld borderline-patiënten waren uitgesloten in de meeste MDMA-PTSS trials). Hierdoor is er weinig directe data. Toch begint men de mogelijkheden te verkennen, met name voor borderline persoonlijkheidsstoornis (BPS). In 2023 is een overzichtsartikel verschenen dat pleit voor onderzoek naar MDMA-geassisteerde psychotherapie bij borderline. De auteurs wijzen erop dat MDMA-therapie veelbelovend is gebleken bij PTSS, dat vaak overlapt met borderline-problematiek, en speculeren dat MDMA mogelijk kan helpen bij de interpersoonlijke en affectieve instabiliteit van BPS. Er lopen inmiddels initiatieven: zo is in Canada/McLean Hospital een fase-1 studie opgestart om MDMA te testen bij volwassenen met BPS, gericht op sociale cognitie en empathie als uitkomst. Daarnaast is in Australië (Monash) een trial geregistreerd die MDMA-ondersteunde dialectische gedragstherapie (DBT) gaat onderzoeken bij borderlinepatiënten. Resultaten daarvan zijn op dit moment (2025) nog niet bekend. Voor andere persoonlijkheidsstoornissen is er nog geen direct onderzoek. Wel is er overlapping: bijv. mensen met vermijdende persoonlijkheidsstoornis zouden baat kunnen hebben bij therapie voor sociale angst (er is een case van psilocybine bij sociale angst gerapporteerd – betrof vermijdende kenmerken, maar niet systematisch). Antisociale persoonlijkheidsstoornis – geen studies, maar sommige theoretici speculeren dat psychedelica empathie kunnen verhogen bij psychopathie, echter dit is zeer omstreden en onbewezen. Narcistische stoornis idem, geen data. Dus de focus ligt nu op borderline als veelvoorkomende en moeilijke stoornis waar nieuwe behandeling welkom zou zijn.
2. Veiligheid: Persoonlijkheidsstoornissen, en met name borderline, brengen uitdagingen mee in veiligheid. Borderline-patiënten hebben vaak chronische suïcidaliteit, stemmingswisselingen, paranoïde stress-ideaties – al deze kunnen potentieel versterkt of onvoorspelbaar reageren op psychedelica. Traditioneel wordt het gebruik bij borderline als hoog-risico gezien; psilocybine is contra-geïndiceerd bij borderline volgens sommige richtlijnen vanwege kans op ontregeling. Dit baseert men niet op empirische ongelukken (die zijn er nauwelijks gerapporteerd, omdat men het simpelweg zelden gedaan heeft), maar op voorzorgsprincipe. Men vreest bijvoorbeeld dat een borderline-patiënt overweldigd wordt door intense emoties in de trip en daarna suïcidaal kan handelen. Of dat de hechtingsdynamiek (sterke idealisatie en devaluatie) richting therapeuten verstoord raakt door zo’n intieme ervaring als MDMA-therapie. Toch zijn er ook redenen om te denken dat het veilig kán onder stringente voorwaarden: In de PTSS-studies zaten ongetwijfeld deelnemers met borderline-trekken (PTSS en BPS overlappen vaak); die doorliepen de MDMA-sessies meestal prima en hadden baat. Langetermijn-follow-ups van PTSS-studies lieten geen hoog suïcidecijfer zien door de therapie. Ook de nieuwe studies zullen veiligheidseisen hanteren: bijvoorbeeld alleen stabiele borderline-patiënten (geen acute crisissen, niet ernstig automutilerend op moment van therapie). MDMA zelf heeft een kalmerend effect op amygdala en bevordert zelfliefde – dat zou borderline-patiënten paradoxaal misschien helpen om even uit hun intense angst en leegte te stappen en inzicht te krijgen. Psilocybine is trickier: borderline gaat soms gepaard met micropsychoses en extreme angst voor verlating; een psilocybinetrip zou zo iemand naar erg duistere plaatsen kunnen brengen zonder goede sturing. Er is voor zover bekend nog geen psilocybinestudie bij borderline (vermoedelijk begint men liever met MDMA vanwege het meer beheersbare emotionele profiel). Samengevat: de veiligheid is ongetest, dus voorzichtigheid geboden. Indien men het doet, moeten er stevige vangnetten zijn: 24/7 bereikbaarheid na sessies, crisisplannen, en integratie via evidence-based therapie (DBT) om emotionele stabilisatie te borgen. Borderline-patiënten zijn gevoelig voor teleurstelling en emotionele intensiteit; een psychedelische ervaring kan die twee factoren vergroten. Dit vergt zeer ervaren therapeuten om veilig te laten verlopen.
3. Therapeutisch effect: Hypothese: MDMA-therapie zou bepaalde kernsymptomen van borderline persoonlijkheidsstoornis kunnen verlichten – zoals de heftige emotionele reactiviteit, trauma-gerelateerde angst, en paranoïde wantrouwen in relaties. In PTSS-behandeling met MDMA zag men dat patiënten beter in staat werden tot emotieregulatie en vertrouwen, aspecten waar borderline ook moeite mee heeft. De plausibiliteit is dus aanwezig. Concreet speculeren onderzoekers dat MDMA binnen een DBT-kader bijvoorbeeld kan helpen de effecten van therapie te “boosten” – door tijdens MDMA-sessies diepe zelfcompassie of inzicht te laten ontstaan, wat vervolgens in DBT verder geïntegreerd kan worden. Mogelijke doelen zijn: verminderen van chronische leegte (MDMA kan een gevoel van verbondenheid geven, wat iemand het inzicht kan geven dat ze in staat zijn warmte te voelen), doorbreken van wantrouwen (MDMA’s toegenomen empathie en openheid kan de therapeutische alliantie enorm versterken, zodat de patiënt eindelijk iemand durft te vertrouwen), en verwerken van onderliggend trauma (veel borderline-patiënten hebben misbruik of verwaarlozing in jeugd; MDMA kan net als bij PTSS helpen dat te verwerken). Psilocybine zou op een andere manier mogelijk nuttig zijn: het kan ego-grenzen doen vervagen en perspectief verschuiven – voor borderline zou dat potentieel kunnen betekenen minder rigide zwart-witdenken en een ervaring van verbondenheid met iets groters, wat de existentiële eenzaamheid verlicht. Echter, daarover is nog minder theoretisch geschreven. Voor andere persoonlijkheidsstoornissen: men kan speculeren. Bij vermijdende persoonlijkheidsstoornis (die sterk overlapt met sociale angst) zou MDMA of psilocybine net als bij sociale angststoornis kunnen helpen openbreken en sociale interactie vergemakkelijken – echter, geen data direct. Antisociale persoonlijkheidsstoornis: zeer controversieel – sommigen dachten dat psychedelica empathie bij psychopathie konden induceren, maar er is ook risico dat het misbruikt wordt of niet aankomt wegens gebrek aan emotionele resonantie (er bestaat een enkel oud geval waar LSD in de 60s bij criminelen is getest, wat fiasco was omdat ze er agressiever van werden of het manipuleerden). Dus dat laat men voor nu met rust. Narcistische stoornis: geen data, maar men zou fantaseren dat een mystieke ervaring narcisten hun nietigheid laat inzien en empathie geeft – wederom, niets bewezen. Kortom: het potentiële therapeutisch effect ligt vooral bij borderline en eventueel cluster C (vermijdend/obsessief-compulsief) persoonlijkheden, door toename van empathie, vertrouwen en flexibiliteit.
4. Risico’s/Contra-indicaties: Borderline specifiek: Contra-indicatie zou zijn een persoon die recentelijk ernstige suïcidepogingen of automutilatie heeft gedaan zonder stabilisatie – die is te kwetsbaar. Ook iemand die geen stabiele therapierelatie heeft of therapie-ontrouw is, is ongeschikt (deze behandeling vereist sterke samenwerking, anders te riskant). Impulsieve verslaving of eetstoornis bij borderline zou eerst behandeld moeten worden voordat men psychedelica overweegt, anders kan het door elkaar gaan lopen (bv. borderline met boulimia: psilocybine zou misschien wel eetdrang beïnvloeden, maar de emotionele labiliteit plus boulimia plus trip kan teveel zijn). Een groot risico bij borderline is suïcidaliteit in de nasleep: stel de persoon ervaart intense emoties in de sessie (bijv. diepe spijt, of overweldigend verdriet) en heeft daarna moeite daarmee om te gaan, dan is er kans op impulsieve zelfbeschadiging. Daarom vereist dit eigenlijk dat men geïntegreerde therapie (zoals DBT) direct paraat heeft, waarin crisismanagement ingebouwd is. Ook moeten betrokkenheid van het sociaal netwerk overwogen worden voor steun na sessies. Een ander risico: idealiseerde devaluatie van therapeuten – borderline cliënten kunnen de MDMA-therapeut als “redder” gaan zien of juist agressief worden als iets tegenvalt. Dit vraagt therapeuten die zeer bedreven zijn in omgaan met die overdracht, anders kan de behandelrelatie ontsporen na de intensiteit van de sessie (denk: patiënt voelt zich ongekend verbonden tijdens MDMA-sessie, maar voelt zich daarna verlaten en dat slaat om in woede). Dit is meer een klinisch risico dan een lichamelijk, maar wel reëel. Contra-indicaties psychotische decompensatie: borderline kan soms kort psychotisch worden bij stress; psilocybine zou dat zeker kunnen triggeren, MDMA minder waarschijnlijk maar toch. Iemand met borderline die ooit langdurige psychoses had zou ik uitsluiten (overlap met schizo-affectief is dan te groot). Fysiek: persoonlijkheidsstoornissen op zich geven geen medische contra-indicaties, dus dat valt mee. Voor andere persoonlijkheidsstoornissen: antisociale PS zou ik eigenlijk als contra-indicatie beschouwen gezien de onvoorspelbaarheid en gebrek aan empathische basis – groot risico dat het niet klikt of zelfs misbruikt wordt (antisocialen kunnen glashard gaan liegen of manipuleren tijdens de sessie, wat het nut teniet doet en gevaarlijk kan zijn). Narcisten kunnen misschien een nare trip krijgen als hun ego “sterft” wat tot agressie of paniek leidt. Daar moet een therapeut op voorbereid zijn. Obsessief-compulsieve persoonlijkheidsstoornis (niet te verwarren met OCD) – die zijn stijfhoofdige mensen die controle willen, die zouden moeite kunnen hebben zich over te geven, wat riskant is dat ze in weerstand blijven steken en een angstige trip hebben. Dus terwijl niet per se uitgesloten, is grondige voorbereiding op controleverlies nodig.
De algemene positie is nu: persoonlijkheidsstoornissen (vooral cluster B) werden als relatieve contra-indicatie gezien voor psychedelische therapie, vanwege bovengenoemde risico’s. Echter, gezien de lijdensdruk en beperkte behandelopties bij borderline bijvoorbeeld, vindt men dat voorzichtig onderzoek gerechtvaardigd is. De aanpak moet dan wel geïntegreerd zijn in bestaande evidence-based therapie, niet losstaand. Samenvattend: MDMA/psilocybine bij persoonlijkheidsstoornissen is experimenteel, potentieel effectief met name bij borderline, maar brengt aanzienlijke risico’s van emotionele destabilisatie mee. Contra-indicaties zijn acute suïcidaliteit, onbehandelde comorbide ernstige stoornissen, en onvoldoende gestructureerde behandelomgeving.
Parafilische stoornissen
(Bijv. pedofiele stoornis, voyeurisme, frotteurisme, seksueel sadisme als stoornis.)
1. Onderzoek: Geen. Er is geen onderzoek bekend dat MDMA of psilocybine inzet om parafiele stoornissen te behandelen. Dit onderwerp is ethisch beladen en klinisch ingewikkeld; de behandelingen voor parafilieën zijn meestal gedragstherapie, aversietherapie, SSRI’s of anti-androgenen, niet psychedelica. Het ligt dus buiten de scope van het huidige psychedelica-onderzoek.
2. Veiligheid: Moeilijk te zeggen in afwezigheid van studies. Op zich zijn parafiele stoornissen niet per se medische condities die fysiek iets veranderen wat relevant is voor psychedelica. Een parafiele patiënt kan lichamelijk gezond zijn, dus MDMA/psilocybine zouden fysiologisch hetzelfde effect hebben als bij een ander. Het psychische veiligheidsaspect is echter delicaat: psychedelica kunnen seksuele beleving intensiveren of vervormen; bij iemand met deviante seksuele fantasieën zou dat tot onvoorspelbare innerlijke ervaringen kunnen leiden. Het is onbekend hoe bijvoorbeeld een pedofiele stoornispatiënt onder psilocybine zou reageren als zijn fantasieën opkomen – mogelijk schuld, angst, of juist genot, geen idee, maar dit kan zeer ontwrichtend zijn. Zonder dat we dit ooit getest hebben, moeten we er vanuit gaan dat veiligheid hier vooral theoretisch besproken kan worden. Er is wel eens opgemerkt dat MDMA in een therapeutische context mensen meer open over hun seksualiteit kan maken; dat zou kunnen betekenen dat iemand zijn parafiele gedachten eerder durft te bespreken, wat therapeutisch wellicht nuttig is maar ook zorgvuldig gemodereerd moet worden.
3. Therapeutisch effect: Onbekend en speculatief. Sommigen hebben geopperd dat psychedelica, door persoonlijke inzichten en empathie, recidive bij bijvoorbeeld seksueel delictplegers zouden kunnen verminderen – door ze empathie voor hun slachtoffers te laten voelen of de oorsprong van hun stoornis te doorgronden. Dit is echter louter hypothetisch en niet zonder controverse (moreel en wetenschappelijk). Er zijn geen empirische aanwijzingen dat MDMA of psilocybine parafiele neigingen vermindert. Het zou misschien net zo goed de seksuele fantasieën kunnen versterken (immers, psychedelica versterken innerlijke belevingen). Voor een dwangmatige parafiele stoornis (bijv. exhibitionisme) zou men zich kunnen voorstellen dat psychedelische therapie helpt onderliggende eenzaamheid of trauma te helen, waardoor de drang afneemt. Maar dit is allemaal onbewezen. Tot nu toe zijn er geen rapporten dat iemand “genezen” is van een parafilie dankzij een trip.
4. Risico’s/Contra-indicaties: Het onderwerp parafilieën raakt aan forensische context. Een groot risico zou zijn als psychedelica ongecontroleerd in die populatie gebruikt worden: iemand met bijvoorbeeld sadistische neigingen zou onder invloed mogelijk impulsiever worden en een ander kwaad kunnen doen. In een gecontroleerde setting (therapiekamer) is dat minder issue, maar als ze het zelf buitenom doen, potentieel wel. Contra-indicatie is sowieso dat de meeste parafiele patiënten niet uit eigen motivatie hulp zoeken tenzij gestuurd, en psychedelische therapie vereist informed consent en bereidheid. Een veroordeelde pedofiel dwingen tot MDMA-therapie zou ethisch onaanvaardbaar en praktisch gevaarlijk zijn. Daarnaast, veel parafiele stoornissen gaan samen met ontkenning en minimale empathie voor slachtoffers. Psychedelica dwingen geen verandering af; als iemand sterk defensief is, kan een trip zeer angstig worden of juist geen doorbraak geven, wat het nut in twijfel trekt en potentieel stress veroorzaakt die de parafilie misschien nog versterkt (als coping). Ook is er reputatieschade-risico: dit is meer een maatschappelijk risico – als men ooit psychedelica zou geven aan, zeg, zedendelinquenten en er gaat iets mis, dan kan dat een enorme backlash geven tegen het hele onderzoeksveld.
Puur medisch zijn er geen specifieke contra-indicaties die anders zijn dan de al genoemde (hart, psychose etc.). Maar vanuit behandelingsoogpunt zou men geen psychedelische therapie toepassen bij parafilieën zolang niet in zeer veilige onderzoekssituatie en zelfs dan uiterst controversieel. Ethisch gezien moet de persoon wilsbekwaam en instemmend zijn, en er mag geen gevaar voor anderen zijn. Aangezien parafiele stoornissen vaak risk-assessment kwesties hebben (terugvalpreventie om anderen te beschermen), is het riskant een onvoorspelbaar element als een psychedelische sessie toe te voegen zonder goed te weten wat dat met hun impulsen doet. Vandaar is dit domein eigenlijk terra incognita en voorlopig een no-go.
Conclusion
Samenvattend: MDMA en psilocybine blijken in gecontroleerde therapiecontext veilig en potentieel effectief voor verschillende DSM-5 stoorniscategorieën, maar dit is sterk stoornis-afhankelijk. Vooral bij PTSS/traumastoornissen (MDMA) en depressie en verslaving (psilocybine) is inmiddels gedegen onderzoek met bemoedigende resultaten qua symptoomreductie en blijvende verbeteringen. Ook bij angststoornissen (met name existentiële angst, sociale angst) worden significante therapeutische effecten gezien onder begeleiding. In al deze gevallen is het gebruik in klinische setting veilig bevonden, zonder ernstige complicaties. Daarentegen zijn er categorieën waar gebruik ontraden of experimenteel is, zoals psychotische stoornissen (risico op psychose-exacerbatie), bipolaire I-stoornis (manierisico), dissociatieve stoornissen (weinig bekend, potentieel destabiliserend), en persoonlijkheidsstoornissen (vooral borderline, waar wel voorzichtig onderzoek gestart is maar met verhoogd crisisrisico).
Cruciaal is dat de veiligheid vrijwel steeds afhangt van strikte uitsluiting van contra-indicaties (geen geschiedenis van psychose of ernstig hartlijden, geen actuele middelenintoxicatie, etc.) en van een gecontroleerde therapeutische context met getrainde professionals. Onder die voorwaarden laten studies overwegend milde, voorbijgaande bijwerkingen zien (zoals serotonerge bijwerkingen bij MDMA en zintuiglijke/perceptuele verstoringen bij psilocybine).
Het therapeutisch effect varieert per stoornis: van symptoomverlichting (bv. minder dwang bij OCD, minder angst bij sociale fobie), via trauma-integratie en verwerking (bij PTSS met MDMA), tot gedragsverandering zoals abstinent worden van verslavende middelen (bij alcohol- en tabaksverslaving met psilocybine). In sommige gevallen is het effect ronduit revolutionair ten opzichte van klassieke behandelingen (PTSS en verslaving springen eruit), in andere is het nog onzeker of marginaal (bv. bij eetstoornissen en persoonlijkheidsproblematiek moet meer onderzoek uitwijzen hoe groot en duurzaam de verbetering is).
Risico’s en contra-indicaties dienen steeds stoornis-specifiek te worden bekeken. Voor elke categorie geldt dat ondeskundig gebruik of toepassing bij foutieve doelgroep risico’s kent: zo kunnen psychedelica latente psychoses ontketenen bij schizofrenie, manieën bij bipolaire gevoeligheid veroorzaken, of emotionele crises bij instabiele persoonlijkheidspatronen triggeren. Cardiovasculaire risico’s zijn een rode draad (MDMA verhoogt hartslag/BP, dus ongecontroleerde hypertensie of recente hartinfarct zijn absolute contra-indicaties). Ook combinatie met bepaalde medicijnen is gevaarlijk – bv. SSRI’s kunnen het effect blokkeren en in combinatie met MAO-remmers is er risico op serotoninesyndroom. Elk onderzoek hanteert daarom stringente selectie.
Specifieke risico’s: bij autisme dient men sensorische overprikkeling in acht te nemen (MDMA kan sterk lichamelijk en emotioneel zijn, wat bij ASS zorgvuldig gemonitord moet) – toch zag men geen ernstige bijwerkingen in de autismestudie. Bij OCD was er zorg over mogelijke verergering van obsessies, maar in de praktijk trad dat niet op; men zag juist geen psychoses of suïcidaliteit ontstaan. Verslavingspatiënten moeten goed ontgift zijn om interacties te vermijden, maar opmerkelijk is dat psychedelica geen verslavingsgedrag lijken uit te lokken – tijdens therapie greep men niet naar andere drugs en men misbruikte de studiemedicatie niet.
Conclusion: Onder strikte professionele begeleiding kunnen MDMA en psilocybine veilig worden ingezet bij bepaalde DSM-5 stoornissen en aanzienlijke therapeutische effecten bereiken, zoals het doorbreken van langdurige klachten of het versnellen van psychotherapeutische processen. Het bewijs is het sterkst voor trauma/PTSS (MDMA) en voor depressie en afhankelijkheid (psilocybine), en zwakker of afwezig voor andere categorieën. Sommige stoornissen (psychotische, bipolaire I, etc.) blijven absolute no-go gebieden wegens risico’s op verslechtering. Het is belangrijk te benadrukken dat deze interventies altijd onderdeel zijn van een breder behandeltraject (psychedelic-assisted therapy) en niet losstaand worden toegepast. Mits juist toegepast, tonen de huidige wetenschappelijke bevindingen dat MDMA en psilocybine voor geselecteerde stoornissen een veilige en veelbelovende nieuwe behandelmodaliteit vormen – met effecten variërend van symptoomreductie tot diepgaande, langdurige gedragsverandering en psychisch herstel, en dit bij afwezigheid van ernstige bijwerkingen of verslavingsrisico’s in de therapeutische setting.
Sources: De hierboven gegeven informatie is gebaseerd op recente klinische onderzoeken en publicaties, waaronder fase-3 studies naar MDMA bij PTSS ucsf.edu, fase-2 studies naar psilocybine bij depressie pubmed.ncbi.nlm.nih.gov en verslaving, en diverse pilotstudies (bijv. MDMA bij autisme trialsjournal.biomedcentral.com, psilocybine bij OCD healio.com, psilocybin for anorexia nature.com). These scientific sources support the stated effectiveness and safety findings in the various disorder categories. For disorders for which there is no direct research, the points mentioned are based on theoretical considerations and general guidelines/warnings from the literature.psychedelics.ucsf.eduen.wikipedia.org. Each application must be individually assessed based on the most current evidence and under the supervision of specialized practitioners.
NB: AI can make errors in reasoning, and further in-depth study of the subjects may be necessary in some areas!
Posted : 15 May 2025 21:06