When SUDs and codependency exist between a couple, the ideologies of codependency can consequently enforce the partner to continue using substances (Vederhus et al., 2019). Symptoms from the substance-using partner can reinforce maladaptive thoughts/behaviors residing in the individual with codependency. For example, codependent individuals may take on the consequences of their partner’s drug usage to minimize the severity of their partner’s disorder (Bortolon et al., 2016). To control the user, someone with codependency is believed to develop an addiction to the partner (Lampis et al., 2017). While these two disorders appear to exacerbate each other, it seems these disorders complement each other in a less apparent way, requiring the need to emphasize the importance and severity of this unhealthy relationship.

Such couple dynamics can be explained within the context of family systems theory, which is a conceptual model that views the family as a behavioral system responsive to forces concerning the maintenance of stability (morphostatic) and change/organization (morphogenic) (Steinglass, 1985). Systems theory emphasizes that one disorder in a couple will affect each person and thus the morphostatic dynamic of a romantic relationship or family. Two disorders can unhinge a family system exemplified by codependent spouses of those struggling with an addiction (Lampis et al., 2017).

In this review, the authors acquired up-to-date knowledge on how psilocybin can treat SUDs and how MDMA has the potential to treat codependency in an intervention that is commonly known as psychedelic-assisted therapy (PAT). Specifically, psilocybin may reduce symptoms of addiction (both chemical and perceptual) to provoke long-term changes for recovery, while MDMA may address the root of negative codependent behaviors to become insightful about one's own issues and their spouse’s addiction. It is proposed that each modality of treatment can accelerate recovery from systemic issues wherein there is both codependency and substance use in a couple. Through research of the pharmacological properties of psilocybin and MDMA and current understanding of their clinical efficacy, the researchers present a therapeutic opportunity using these psychedelics to aid in couples therapy.

In 2023, 3.1% of people (8.9 million) misused opioids in the past year, which is similar to 2022 and 2021. Of people aged 12 or older, 134.7 million used alcohol in 2023, and 61.4 million people (or 45.6%) had engaged in binge drinking in the past month (SAMHSA, 2023). Notably, American Indian, Alaska Native, and other Multiracial people were more likely than other racial or ethnic groups to have used substances or to have had a substance use disorder (SUD) in the past year (SAMHSA, 2023). A SUD is seen as a continuance of use despite any biological, social, or psychological consequences leading to impaired control of risky misuse and chemical or perceptual dependence (American Psychiatric Association (APA), 2023). SUDs are one of the most common mental health issues in the United States, with many reluctant to undergo treatment (SAMHSA, 2023). Consequently, SUDs negatively affect many people’s lives without them even recognizing the gravity of their situations. SUDs not only disrupt physical and mental health but also contribute to significant social and relational challenges, further exacerbating the individual's overall well-being. The typical unpredictability and instability caused by SUDs often lead to conflict, isolation, and strained communication, making it difficult for individuals to maintain healthy, supportive connections (West & Brown, 2013). Thus, there is an additional element to substance abuse that extends beyond the individual struggle.

Codependency often arises from early childhood experiences, particularly in families with dysfunctional patterns such as neglect or emotional abuse, where individuals learn to prioritize others' needs over their own for a sense of self-worth and emotional security. This behavioral pattern can develop to cope with or survive in an environment where love and approval are conditional (Orbon et al., 2021). In the context of monogamous relationships, especially in instances of SUDs, individuals struggling with codependency have a direct impact on the well-being of their partner. Systems therapy is a sound approach to the problematic dynamic with SUDs and codependency, and psychedelic-assisted psychotherapy may show promise as a catalyst in the therapeutic process.

Psychedelics are a group of drugs that alter perception, cognition, and consciousness, often provoking mystical or awe-inspiring personal experiences, and may be an effective treatment for SUDs and other psychiatric disorders (Aixala et al., 2018; DiVito & Leger, 2020; Dos Santos et al., 2016). Psilocybin, the psychoactive compound found in what is commonly known as “magic mushrooms”, displayed initial success in the treatment of psychiatric problems such as anxiety and depression in the 1960s, which was marketed as Indocybin® in the United States and numerous other countries (Johnson et al., 2014). Later legislation classified psilocybin as a Schedule I illicit drug, which prevented researchers from examining the clinical utilities of this naturally occurring substance (DiVito & Leger, 2020). After many years, psilocybin has begun to be a treatment prospect for not only depression and anxiety but also SUDs (Johnson et al., 2017).

3,4-Methylenedioxymethamphetamine (MDMA) is similarly demonstrating success in the treatment of post-traumatic stress disorder (PTSD) symptoms and expressing the possibility of addressing all trauma-related disorders and symptomatology (Edut et al., 2011; Sessa et al., 2019). With that, psychiatrists are increasingly emphasizing the role played by early psychological and environmental adversity in a range of mental disorders beyond that of PTSD (Sessa et al., 2019). While there is plentiful research on MDMA for PTSD, there is currently no clinical data on using MDMA for other disorders or conditions, such as codependency. Julie Holland, MD accounts in one of her best-sellers Good Chemistry: The Science of Connection, From Soul to Psychedelics (2020), tells an anecdotal situation wherein a spouse underwent MDMA-assisted treatment to further understand her husband’s psychological issues and the relationship’s subsequent transformation. The spouse, previously exhibiting symptoms of codependency, appeared emotionally inhibited prior to the experience; however, these restraints seemed to ease following MDMA administration, leading to lasting change in the couple (Holland, 2020). As anecdotal stories and clinical research expands, the potential to treat SUDs and other psychiatric conditions continues to develop, underscoring the need for further scientific and theoretical exploration.

Family Dynamics of Addictive Behaviors and Codependency

Substance abuse is a major public health concern contributing to the global burden of disease by negatively affecting the well-being, health, and safety of users. Sharma and colleagues (2019) estimate that over 100 million people are affected by a family member’s substance use and suffer significant stress and consequential trauma stemming from psychosocial and physical detriments. Ólafsdóttir et al. (2020) discovered that a family member’s SUD results in the spouses and siblings feeling hopelessness or rage in addition to the general psychosocial, physical, and behavioral detriments. Interestingly, partners experiencing feelings of isolation and loneliness have an increased vulnerability to engaging with their partner to meet the needs of connection (Naylor & Lee, 2011). These studies in particular indicate that the partners of substance users go through a multiplicity of challenges that affect overall wellbeing, and many argue these can be traumatic experiences.

A substance use disorder in families is associated with shifts in a family’s power dynamics, rules, roles, and structure—among other adaptations—that negatively impact family member health and well-being (Bradshaw et al. 2016). Family systems theory suggests the family is a system with complex, interrelated, and interconnected influences. Therefore, problematic substance use behavior of a family member can throw the family into a state of disequilibrium and disturb family functioning. Family members attempt restoration of balance, which may result in deficits of physical and emotional health. Moreover, changes in personal relationships occur, which negatively affect their quality of life (Bortolon et al, 2016) manifesting a phenomenon known as codependency.

Codependency and codependent behaviors walk a fine line between positive and negative. Positive codependent behaviors can be conceptualized as natural empathetic or altruistic tendencies that do not impact the general well-being of others, while negative codependent behaviors can be viewed as actions that not only reduce the sustainability of well-being but also put one’s own needs at risk. Individuals with negative codependency (stated as “codependency” moving forward) frequently exhibit difficulty in setting boundaries and/or voicing their own needs because of low self-esteem, emotional dysregulation, and self-blame (Bortolon et al., 2016). Notably, whether it be conscious or unconscious, many who struggle with codependency create attempts to derive a sense of purpose through relationships (Lampis et al., 2017). Codependency can then enable drug users and their family members to engage in mutually destructive habits and maladaptive coping strategies to maintain a sense of balance or homeostasis.

Dennis and Champlin (2021) examined the effect of substance use on the family and found that substance use disturbs each member of the family uniquely, and it’s been found that difficulties establishing boundaries and impaired life satisfaction are effects felt by the non-using partner. Evgin and Sümen (2021) investigated (n=292) the relationship between neglect and abuse behaviors experienced during their childhood with codependency, and the characteristics that manifest are those of codependent attributes. Findings from the study revealed a positive relationship between neglect and abuse behaviors that led to trauma in childhood, and codependency resulting in low self-esteem and depression. In another study, it was concluded that negative or maladaptive codependency diminishes the integrity of a couple dynamic, especially when the opposing partner is struggling with substance abuse (Bortolon et al., 2016). Overall, according to Happ and colleagues (2023), it can be stated that the more codependent individuals are, the more problematic their intimate relationships are found to be. The researchers’ results also support the idea that codependency is a specific, largely stable attitude that determines a person’s perception and behavior relating to others in a family system. In turn, this phenomenon enforces negative coping forms and results in reduced life satisfaction.

Very few individuals with codependency receive treatment because it is rarely conceptualized as a disorder and, therefore, infrequently diagnosed (Bacon & Conway, 2023). Major treatments for addiction focus on the person struggling while using family members as a social support system (Kourgiantakis & Ashcroft, 2018), though there is one question that needs to the answered: if family members can be just as if not more distressed than the substance users, what will be the quality of care or support offered to the whole family? Moreover, can this improve treatment outcomes? By combining PAT treatment for individuals with a SUD as well as an individual demonstrating codependent symptoms, professionals can treat the whole system, which gives a greater chance for the system to change, for the whole is greater than the sum of its parts (Von Bertalanffy, 1972). That said, effective family- and partner-inclusive SUD treatment is underutilized, despite its usefulness in promoting transparency, maintaining treatment adherence, and sustaining recovery (SAMHSA, 2021). This calls for the need to provide comprehensive treatment that treats both members in a romantic partnership.

Psilocybin and Treating Addictive Disorders

The history of ceremonial psychedelic use is extensive, and psilocybin has remained particularly fascinating among the classic hallucinogenic medicines. Psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) is the phosphorylated ester and essential psychoactive compound contained in “magic mushrooms” (Dos Santos et al., 2016; Moliner et al., 2023; Tagliazucchi et al., 2014). Psilocybin has the potential to be an inspiring remedy in its capacity to rewire and reconnect regions of the brain that were once inhibited by neurological dysfunction (Johnson et al., 2017). Serotonergic hallucinogens generate modifications in perception, cognition, and behavior, having antidepressant, anxiolytic, and antiaddictive properties (Carhart-Harris, 2007; Carhart-Harris and Nutt, 2014; Dos Santos et al., 2016; Roseman et al., 2014). While it is not entirely distinct which neuronal foundations are related to these drug-induced occurrences, it is known that extra-pharmacological factors known as set and setting greatly form experiences (Borkel et al., 2024). Congregating evidence suggests the value of a psychedelic experience is predisposed by circumstance, including mentality, expectancies, and environmental influences (Griffiths et al., 2011; Madsen et al., 2019; Preller et al., 2018; Smigielski et al., 2019).

Psilocybin is listed on the Schedule I drug class, indicating it has a high propensity for addiction, though no true risk of dependence has been reported (Rucker et al., 2016). While existing evidence indicates current pharmacological treatments for SUDs have limited effectiveness (Oliva et al., 2011), numerous remedies (Disulfiram, Naltrexone, Nalmefene, and Acamprosate) have been approved by the FDA for the treatment of alcohol use disorder (AUD) and are available in most countries across the globe (Heikkinen et al., 2021). One of the overarching goals of this review is to emphasize the need for a novel intervention that may demonstrate greater efficacy with the same principle: using a substance to help treat a SUD.

Existing evidence shows psilocybin is effective in the treatment of several conditions, such as depression and anxiety (Carhart-Harris et al., 2016; Carhart-Harris et al., 2018; Griffiths et al., 2016). Notably, substance abuse and dependence have similar neurocognitive tendencies observed in conditions like major depressive disorder, exacerbating perceptual and neurological inclinations to use substances, hence the high rate of comorbidity (Calarco & Lobo, 2021; De Veen et al., 2017). Recent studies (Carhart-Harris et al., 2018; Griffiths et al., 2016; Noorani et al., 2018) have confirmed the safety and efficacy of psilocybin as an adjunct to therapy in the treatment of both major depression and addictive disorders. Outside of experiential data regarding psilocybin effectiveness for addictive and depressive symptoms (Carhart-Harris et al., 2018; De Veen et al., 2017), there is a parallel in the way psilocybin pharmacologically addresses depression and cognitive dysfunction from substance use, which reinforces psilocybin’s capacity to address co-occurring disorders that may also arise from problematic relationships (De Veen et al., 2017; Yücel et al., 2007). This may yield future discussion on psilocybin’s role following differential diagnosis and symptomologies that do not meet a diagnosis.

Several published trials have been concluded investigating the treatment of SUDs utilizing PAT with psilocybin, focusing on a range substances of abuse (e.g., alcohol, nicotine, opioids, cocaine, and other amphetamines) that demonstrate significant changes in use (van der Meer, et al., 2023) For example, Johnson et al. (2017) reported that 67% of participants confirm smoking abstinence 12- and 30-months following psilocybin administration merged with psychotherapy, respectively indicating the effectiveness of psilocybin in smoking cessation. One pilot study of psilocybin as an adjunct in smoking cessation treatment resulted in remarkable rates of abstinence (80% at 6-month follow-up) (Johnson et al., 2014). Similarly, a proof-of-concept study found a significant increase in abstinence among alcohol dependent patients 36 weeks after receiving psilocybin (Bogenschutz et al. 2015). This confirmed the clinical utility of psilocybin in the treatment of psychiatric conditions (James et al., 2020; Sessa, 2019), yielding a recommendation that states should consider rescheduling psychedelics from Schedule I to allow for their use in clinical and naturalistic environments. The authors in this case believe psilocybin could be the best treatment for addictive disorders, considering the variables in current pharmacology. Researchers have reported that such treatment had no serious side effects that could warrant medical attention (Carhart-Harris et al., 2018; Carhart-Harris et al., 2016), and analyses have shown no true danger to safety under clinical supervision (Meshkat et al., 2025). Rather, any adverse effect would be a result of a disturbed set and setting groundwork mentioned earlier.

MDMA in Therapy

3,4-Methylenedioxymethamphetamine (MDMA) acts as an indirect serotonin agonist (Roseman et al., 2014), inducing serotonin release from neuronal endings and inhibiting its reuptake. In addition, MDMA is a potent releaser of oxytocin, dopamine, and norepinephrine (McGregor & Bowen, 2012). It does not alter consciousness in the same fashion as classic psychedelics (psilocybin, mescaline, lysergic acid diethylamide, N, N, dimethyltryptamine) and induces an acute euphoria (Roseman et al., 2014). MDMA is not considered to be a classic psychedelic. Although, like psilocybin, its subjective effects are known to be significantly mediated by serotonergic mechanisms.

Though psilocybin has more profound effects on global brain function, MDMA still has some marked effects on functional connectivity in the brain, which could be associated with a couple’s responsiveness to the proposed intervention (Dos Santos et al., 2016; Holland, 2020; Sessa et al., 2019), or at least the individual with codependency. MDMA, in combination with psychotherapy, is reported to have significant therapeutic potential for reducing symptoms of post-traumatic stress disorder (PTSD) (Amoroso & Workman, 2016; Riaz et al., 2023). The authors postulate that MDMA may be efficacious in treating individuals with codependency, especially in the context of those with past trauma, being used to promote systemic resilience in the context of family systems (Sessa et al., 2019; Holland, pp. 39−46, 2020). We explore how this substance, in concert with therapy, may be capable of diminishing codependent traits in the spouse of one struggling with a SUD. The assumption that MDMA could treat codependency derives from the notion that codependent behaviors overlap with psychosocial issues associated with PTSD and Adult Children of Alcoholics (ACoAs) (Bacon et al., 2018; Haverfield & Theiss, 2014). According to Sessa et al. (2019), twenty patients with treatment-resistant PTSD received either two to three sessions of MDMA or a placebo. At 2-month and 12-month follow-ups, “83% of the experimental group no longer met the criteria for PTSD, compared with just 25% of the patients in the placebo group.” No neurocognitive effects were reported after the follow-up. PTSD symptoms were eliminated for up to 6 years without having any further doses of MDMA.

MDMA: A Solution to Codependency

There are no universal definitions or diagnostic criteria concerning codependency in the DSM-5-TR (APA, 2022), though some research identifies it as similar to trauma-related disorders or as trauma symptoms (Almond and Allan, 2019; Bacon et al., 2018; Haverfield & Theiss, 2014). A lack of personal understanding and sense of self, a continuing pattern of extreme, relational, emotional, and occupational discrepancy, and an attribution of current issues to parental abandonment and control from childhood is prevalent in these individuals (Bacon et al., 2018). This sense of abandonment and control ultimately makes one feel duality or split, causing an over-adaptation to environments and relationships to attain a feeling of safety and belonging (Bacon et al., 2018). Life experiences, including the subtleties, shape the way one defines the world and oneself. Similar symptoms are expressed by individuals who were raised by parents who struggled with substance use, also referred to as adult children of alcoholics (ACoAs), and this upbringing can induce prolonged traumatic experiences that disturb development and perception of the world, leading to codependent tendencies (Haverfield & Theiss, 2014). There is weight in expanding the effectiveness of MDMA in therapy to treating other trauma-related disorders since codependency symptoms tend to align with the psychosocial problems of PTSD (Almond and Allan, 2019). However, there are several etiologies of codependency, and such does not exclusively include experiences of trauma.

The codependent behaviors and dysregulated emotions that arise make it difficult for couples to bond, presenting a challenge for individual survivors of trauma as fastened relationships are quintessential to resiliency (Almond & Allan, 2019). In an article by Johnson (2012), he argues that the security within a relationship’s bond creates a type of haven that facilitates emotion regulation in trauma survivors, especially when emotions like anger and fear are met with a positive enhancement to the self and relationship. Therefore, “if a person’s connection with significant others is not part of the coping and healing process, then inevitably it becomes part of the problem,” and such can be a basis of re-traumatization (Almond & Allan, 2019; Johnson,2012).

A great deal of the aforementioned issues with codependency could be diminished with MDMA-assisted psychotherapy under the right conditions. Referencing some of the pharmacological properties of MDMA, and the psychical reflections of this chemistry, occupation of 5-HT1A and 5-HT1B receptors diminishes feelings of depression and anxiety and downgrades the amygdala fear response (Green et al., 2003; Roseman et al., 2014). Thus, increased levels of self-confidence can make revisitation of emotionally reacting memories tolerable. In other words, revisiting memories and situations that typically prompt emotional reactivity is possible not only with a therapist but, consequently, with one’s partner. Positive mood can be attributed to increased feelings of closeness, increased empathy, and greater compassion for oneself and others (Hysek et al., 2013). Furthermore, increased levels of noradrenaline and dopamine induce a state of arousal and awareness (Rothman et al., 2001), which motivates engagement in therapy and the likelihood of fear extinction (Sessa et al., 2019). Alpha-2 receptors (densely located in the sympathetic nervous system) contribute to MDMA's effects on thermoregulation, playing a role in the paradoxical effect of relaxation/sedation (Giovannitti et al., 2015), which could be constructive regarding trauma-induced hypervigilance. The short duration of the experience makes its use clinically manageable and thus appealing. It enriches bonding and states of empathy, allowing users to approach and intentionally process emotionally traumatic memories (Almond & Allan, 2019; Sessa et al., 2019).

Recalling painful emotional memories is difficult and can produce overwhelming negative affect that accompanies avoidance to circumvent the heaviness of these feelings. Unless unpacked, these issues can intensify personal struggles as well as exacerbate existing issues within a family system (Bacon et al., 2018). Indications of trauma, such as emotional dysregulation, hypervigilance, and angry outbursts or irritability, unsurprisingly impact one’s relationship with others and understanding of symptoms like substance misuse in a partner (Lampis et al., 2017). If MDMA one day proves to be a viable intervention for treating codependency and psilocybin for SUDs, a family system could have the opportunity to be uniquely restored through individual clinical practices that can be integrated as a couple in therapy.

Clinical Implications

In the therapeutic process, MDMA could be used as an aid to facilitate the processing and sharing of memories, events, perceptions, and emotions with the therapist and eventually their partner (Wagner et al., 2017). This process of breaking down emotional barriers may mirror relational barriers being taken down, fostering a more meaningful connection within the family system/romantic partnership. Current research has demonstrated that, “MDMA may catalyze therapeutic processing by allowing participants to stay emotionally engaged while revisiting traumatic experiences without being overwhelmed by anxiety or other painful emotions” (Wagner et al., 2017), allowing for the shared experience and open expression of fear, grief, and anger as part of the therapeutic process (Almond and Allan, 2019). Several clinicians and researchers have emphasized that MDMA has caused increased empathy for oneself and others, with less defensiveness and a strengthening of the therapeutic alliance (Almond and Allan, 2019). Taken together, the above factors could provide the opportunity for a curative emotional experience that appears to complement an emotionally focused methodology. The emotion-focused therapy (EFT) model, as well as family systems theory, has specific therapeutic goals: regulate affect, create moments of sharing vulnerabilities so a new meaning can be attained through corrective experience of safe connection, and integrate the revised view of self/other (Johnson, 2012). It appears MDMA may catalyze the process in achieving these goals in a novel yet direct manner.

Carbonaro et al (2016) found that, depending on the dose, individuals injecting psilocybin can experience a negative impact, such as aggression or violent behavior, which may require medical attention. However, let it be known that such negative impacts were not reported in studies conducted in laboratory settings, which supports the important notion of “setting”. This further suggests that medically supervised administration of psilocybin would be safe for use (Carhart-Harris et al., 2018; Carhart-Harris et al., 2018). Furthermore, the above material emphasizes that psilocybin is not only safer than current pharmacological medications, but the lack of dependence and significant reduction of interventions to accomplish the same goal (abstinence or control over usage) makes it medically attractive. Similar to MDMA helping one reach the goals of the EFT model and family systems, the empathogenic effects of psilocybin could also be a catalyst for healing in this regard (Pokorny et al., 2017). The authors of this paper suggest this therapeutic opportunity would entail each partner undergoing individual psychotherapeutic sessions – one taking psilocybin for their addiction, the other MDMA for codependency – and then reconvening to couples therapy for integration. Lastly, it should be noted that individual services, couples services, and PAT in general may be costly beyond clinical investigation if not insured, which poses several ethical dilemmas such as availability and accessibility.

Inconsistencies in Literature

While there is not abundant research regarding psychedelic-assisted couples therapy and treatment, there are still some gaps in the information provided that should be addressed. Specifically, lack of open-label designs and small sample sizes prevent psilocybin's efficacy from being definitive. Moreover, from the client-level standpoint, the level of motivation is a confounding factor (Johnson et al., 2017). Subjective effects are also mediated by the user's personality, expectancy, and social-environmental dynamics, and not entirely by psilocybin’s pharmacology (Studerus et al., 2012). Also, the prevention of adversity may be somewhat challenging as side-effects or distress from psilocybin are conditional on expectations and setting (De Veen et al., 2017). MDMA is continuing to show efficacy for disorders like PTSD with few holes regarding causation, and recent issues concerning ethics in MDMA-assisted therapy clinical trial data yield the need to restructure trial methodology. Another issue is that there are no clinical trials nor much literature on the use of MDMA for codependency, though the researchers hypothesize MDMA to be efficacious in treating most, but not all, trauma-induced or related disorders. The authors reinforce this ideology by recommending research be conducted on MDMA's effectiveness in treating codependency. The Multidisciplinary Association for Psychedelic Studies (MAPS) recently concluded its trials of MDMA-assisted psychotherapy for PTSD (Edut et al., 2011; Sessa et al., 2019). However, there were some ethical concerns related to the methodology and analysis, which raised questions about its true effectiveness, compelling researchers to start from scratch and reevaluate whether MDMA will be a reliable intervention for PTSD.

Contrary to the findings reported by the studies mentioned above, in using animal models to test the effect of psilocybin in alcohol relapse, Meinhardt et al. (2020) found that psilocybin did not have a long-lasting impact on the alcohol deprivation effect. This indicates that psilocybin-assisted treatment may not be as influential on neurocognitions concerning alcohol use disorder (AUD) and other SUDs. However, inconsistencies in clinical data can be attributed to the methodological differences. For instance, while all the previously reported studies used human samples, Meinhardt and colleagues (2020) used animal models and did not use any psychosocial intervention in addition to the psilocybin to combat social norms with participants. One may consequently argue that the persistent reduction of substance use disorder symptoms is facilitated by the psychosocial interventions used in combination with psychedelic treatment, and not just the mere effects of psychedelics. The frequency of psilocybin-assisted psychotherapy sessions should be researched further, as well as the depth of preliminary and integration sessions. Despite the restrictions on the use of psychedelics, evidence emanating from old and recent studies points to their clinical utility in the treatment of several psychiatric conditions. The available evidence suggesting its efficacy requires that researchers continue to examine the specific functions to further understand the empathogenic and antiaddictive effects of psilocybin.

Codependency involves a perceived sense of closeness that, in many ways, may be more of a maladaptive, enmeshed bonding. Additionally, codependency can be associated with partners being over-trusting, leading to extending trust when such trust is not warranted. Thus, further discussion should be had on the nature of a codependent relationship and the unique, influential roots within each dynamic. While increased empathy and compassion are likely a good thing, codependency has also been associated with what might be considered “pathological altruism” (Oakley, 2011). Such should be clearly defined before assessing for codependency and labeling participants in clinical research.

Clinical Investigations: Risks and Considerations

Future researchers that seek to implement the proposed intervention may want to consider the following: the therapeutic alliance in the context of couples therapy with corresponding individual sessions and the role of psychedelics in the patient-therapist relationship; the impact of adverse psychedelic experiences in individual sessions and the consequential effect of the narrative and trajectory of couples therapy sessions; and the proper dosage of psilocybin and MDMA, frequency of the dosage (if appliable), along with preparation and integration sessions that surround PAT sessions in addition to general protocols that mediate “set” and “setting”.

It may be emotionally challenging or exhausting if the same therapist is not conducting every session if not involved in each stage, especially when relational elements (i.e., needs, difficulties, and goals) are not held throughout treatment. Building this alliance is quintessential to effective care, and the proper protocols highlight retaining relational elements throughout the session, involving the same therapist throughout all sessions, and integrating the patient’s regular therapist in each process (Villiger, 2024). There should also be space to acknowledge any negative impact of individual psychedelic-assisted services and the influence on the continuity of care, as well as postulating the impact of joint psychedelic-assisted interventions. Also, while the concepts presented are certainly intriguing, is there a possible risk that MDMA unintentionally increases unwarranted trust, enmeshment bonds, and aspects similar to pathological altruism? What of the paradox behind using a psychedelic (a substance, nonetheless, despite little addictive propensity) to treat a SUD, and risks behind lack of education about the “proper” use of psilocybin? In addition, it should be noted that common dosages for psilocybin in clinical research tend to be from microdosing (1–5 mg) to 20–40 mg/70 kg, while MDMA dosages tend to be around 75–125 mg in most recent phase 3 clinical trials (Meshkat et al., 2025; Wolfgang et al., 2025). Based on reviews of clinical trials, the pattern of services should consist of several preparation sessions that emphasize goals and the therapeutic alliance, then having a medication session followed by several integration sessions that focus on implementation and prolonging the effects/benefits of a PAT session (Chisamore et al., 2024). That being said, there is no statistically significant association between therapy hours and treatment outcomes, wherein more research needs to be done on the therapeutic component in treatment (Hultgren et al., 2025). Implementing this proposed intervention for clinical research would fall under the FDA guidelines for psychedelic drug research under the guidance document “Psychedelic Drugs: Considerations for Clinical Investigations” (Center for Drug Evaluation and Research, 2023), containing a multitude of protocols essential to conducting this type of research.

Conclusion

One purpose of this literature review was to highlight the medicinal properties and benefits of psilocybin and MDMA – substances that were once stigmatized to the point to which mere research on psychedelics was frowned upon. Now, MDMA is on beyond its Phase 3 trial for PTSD treatment and continues to underline the need to look in the direction of other disorders such as codependency (Edut et al., 2011; Sessa et al., 2019). While psilocybin is yet to reach large-scale clinical trials, the promising results from small-sample trials (Johnson et al., 2014; Johnson et al., 2017) should incite researchers to continue investigating this compound for a range of psychiatric issues. The larger purpose of this review was to underscore the potential of a psychedelic-assisted therapeutic intervention in the context of couples therapy, which should be further researched and tested. Psychedelics in therapy are complicated and unorthodox in and of itself, and postulating similarly novel, unorthodox, and evidence-based forms of family systems therapy to accommodate psychedelic science may be warranted. The authors suggest that the process, from a clinical standpoint, would entail each partner undergoing individual psychotherapeutic sessions – one taking psilocybin for their addiction, the other MDMA for codependency – and then reconvening to couples therapy for integration throughout the therapeutic process. Based on the information provided surrounding family systems theory, the idea could be a viable option for addressing issues in family systems in a reduced yet transformative period.

As more research unfolds, the integration of psychedelics into family systems therapy could catalyze therapeutic practices, offering a pathway to disrupt deep-rooted patterns of dysfunction and promote long-term relational healing through practice. By leveraging the unique properties of psilocybin and MDMA in psychotherapy and family therapy, clinicians may be able to facilitate intimate connections and mutual understanding between partners, aligning with the morphogenic goals of family systems theory to promote adaptive change. Future studies should prioritize rigorous clinical trials to establish standardized protocols, ensuring that such contemporary interventions are both safe and effective for diverse populations grappling with the intertwined challenges of SUDs and codependency.