Abstract
Background and aims
Psychedelic and MDMA-assisted psychotherapy are at the forefront of new treatment models for mental illnesses such as PTSD and depression, as well as improving well-being. Mindfulness meditation and loving-kindness meditation have also gained research traction, showing promise for enhancing emotional regulation and psychological well-being. This paper explores the therapeutic convergence of these modalities, highlighting their neurobiological, psychological, and phenomenological overlap, and suggesting potential bidirectional synergy as a foundation for psychedelic or MDMA-assisted therapy.
Methods
A narrative and theoretical review of the current literature was conducted, examining the neurobiological, psychological, and phenomenological effects of MDMA, psychedelics, and meditation. Studies focusing on their potential synergy and mechanisms of action were prioritized and used as a backing for a theoretical framework.
Results
Psychedelics may improve psychological flexibility, prosocial behaviors, empathy, and neuroplasticity. Meditation research suggests similar benefits, including enhanced decentering capacity, emotional regulation, and well-being. Both modalities influence overlapping neural circuitry, particularly the amygdala, hippocampus, and default mode network. Integrating meditation with MDMA or psychedelic-assisted therapy may stabilize insights gained during altered states of consciousness, promote sustained therapeutic benefits, and minimize distress during therapy.
Conclusions
The convergence of meditation and psychedelics or MDMA-assisted therapy is a novel and promising approach for enhancing mental health treatments. Future research should investigate structured protocols combining these modalities, focusing on optimizing “set and setting” and long-term integration practices.
Introduction
Despite robust evidence of human consumption of psychedelic compounds and the capacity for mystical experiences invoked by various methodologies throughout ancient history, only in recent years has the resurgence of psychedelic research allowed for further discoveries about their potential utility in promoting well-being and treating multiple psychiatric conditions. Much work continues to examine the neural correlates, safety, efficacy, and therapeutic potential of non-ordinary states of consciousness (NOSC) induced by classic psychedelics and 3,4-Methylenedioxymethamphetamine (MDMA), as well as meditative states. Hypotheses regarding the underlying mechanisms behind their therapeutic value, which conditions they can treat, and defining the optimal set and setting parameters continue to be tested and refined. There have also been exciting findings in understanding the salutogenic mechanisms and neurobiological correlates of meditative states and subjective improvement in individuals with various disorders such as depression and anxiety. Since 2021, several review papers have examined the potential synergy and commonalities between meditative states and psychedelic states, particularly concerning mindfulness-based interventions (MBI) and classic psychedelics, which include compounds such as psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), and mescaline (Chambers, Stoliker, & Simonsson, 2023; Eleftheriou & Thomas, 2021; Holas & Kamińska, 2023; Ko, Knight, Rucker, & Cleare, 2022; Payne, Chambers, & Liknaitzky, 2021). Throughout this reading, the term “psychedelics” will specifically refer to these compounds and exclude MDMA. Despite frequently being lumped in with psychedelics, particularly in media, MDMA has subtle differences in its mechanism of action and phenomenology. It is often referred to as an empathogen (“empathy generating”) or an entactogen (“producing a touching within”) due to its ability to enhance feelings of empathy, self-compassion, and emotional connection, showing promise for the treatment of post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) among other conditions (Nichols, 2022; Richards & Barnard, 2016; Sessa, Higbed, & Nutt, 2019). In contrast, psychedelics, which are often referred to as entheogens (“To Generate the Divine Within”) due to their ability to invoke mystical experiences and NOSC, are characterized by a deeply felt transpersonal connection to the universe, positive mood, ineffability, revelation, transcendence of time and space, and the breakdown of the ego structure of the mind (Mithoefer, Grob, & Brewerton, 2016; Richards & Barnard, 2016).
Few review papers have directly included MDMA in their comparative analyses. Moreover, most have focused solely on mindfulness meditation rather than loving-kindness meditation. The purpose of this paper is to examine and compare the effects of meditation, MDMA, and psychedelics. Additionally, this paper explores the potential synergies between different types of meditation with psychedelic or MDMA-assisted psychotherapy.
Effects of MDMA and psychedelics
Pharmacology
After oral administration, MDMA's subjective effects occur 30–90 min after oral ingestion (Grob & Grigsby, 2021). The peak effects usually occur 90–120 min following administration, with a total duration of action ranging from 3 to 6 h. Its half-life elimination is around 8–9 h (Grob & Grigsby, 2021). MDMA exerts its effects on the central nervous system primarily by increasing the endogenous release of serotonin (5-HT) and, to a lesser degree, norepinephrine (NE) and dopamine (DA) via reuptake inhibition (Carhart-Harris et al., 2015; Green, Mechan, Elliott, O'Shea, & Colado, 2003). In contrast, psychedelics bind with greater affinity and stimulate 5-HT2A receptors directly, while MDMA has a much weaker affinity for 5-HT2A receptors (Green et al., 2003; Roseman, Leech, Feilding, Nutt, & Carhart-Harris, 2014). Evidence also suggests effects from MDMA via increased oxytocin, prolactin, cortisol, brain-derived neurotrophic factor (BDNF), and arginine vasopressin (AVP) (Feduccia & Mithoefer, 2018; Parrott, 2009). Following oral ingestion, psilocybin is converted to the psychoactive drug psilocin (Grob & Grigsby, 2021, p. 184). Onset occurs approximately 30 min after ingestion (Grob & Grigsby, 2021, p. 185). Peak effects occur at 1–1.5 h; the total duration of effects lasts 6–8 h (Grob & Grigsby, 2021, p. 185). Other psychedelics like LSD, DMT, and mescaline each have unique pharmacodynamic and pharmacokinetic profiles, and the route of administration also alters these profiles.
Phenomenological and psychological effects
MDMA is known to alter subjective experience through changes in mood, empathy, emotional openness, and prosociality, which correlate with increased release of 5-HT, NE, DA, and possibly oxytocin (Hysek, Domes, & Liechti, 2012; Hysek et al., 2013; Sessa et al., 2019). As its street name, “Ecstasy,” suggests, mood alterations are often characterized as excited, euphoric, and positive, likely mediated by these molecules (Feduccia & Mithoefer, 2018; Holas & Kamińska, 2023; Hysek et al., 2012). Both psychedelics and MDMA produce increased feelings of empathy and compassion for self and others (Holze et al., 2020; Hysek et al., 2013). In one study, LSD produced greater rates of ego dissolution and emotional excitation compared to MDMA, potentially suggesting different mechanisms (Holze et al., 2020). Hysek et al. (2013) demonstrated that MDMA enhances emotional empathy and promotes prosocial behavior by decreasing reactivity to threatening stimuli and increasing responses toward rewarding social stimuli. A study of recreational users proposes that one mechanism of action of MDMA in psychotherapy might be related to its capability to improve how individuals perceive and treat themselves (Sunjeev et al., 2015). Overall, MDMA and psychedelics may produce positive internal attitudes, greater compassion towards oneself, and a predilection for increasing personal values focused on collective being and social connection to others in subtly different ways.
MDMA can promote fear extinction and decrease psychological defensiveness (Feduccia & Mithoefer, 2018; Grob & Grigsby, 2021; Sessa et al., 2019). While MDMA can cause acute anxiety and somatic discomfort in some cases, psychedelics also have the potential to cause distressing and challenging experiences, colloquially referred to as “bad trips” (Gashi, Sandberg, & Pedersen, 2021; Taylor, Maurer, & Tinklenberg, 1970). These could be related to mechanisms involving psychological defenses in response to the disorienting ego dissolving aspects of the experience, traits such as neuroticism, and how individuals cope with stress and anxiety (Barrett, Johnson, & Griffiths, 2017). Mitigation focuses on the importance of preparation before the experience and optimizing “set” (the preparation, attitudes, beliefs, intentions, and psychological state of the individual) and “setting” (the physical environment, the therapeutic relationship, and the social support) (Dyck & Elcock, 2020; Johnson, Richards, & Griffiths, 2008). A well-prepared individual without a history of bipolar disorder or a thought disorder who feels safe is most likely capable of experiencing an increase in the personality trait of Openness, less defensiveness, and navigating difficult emotions or memories while generating new insights under the influence of psychedelics (Carhart-Harris, Kaelen, et al., 2016; Lebedev et al., 2016; MacLean, Johnson, & Griffiths, 2011; Payne et al., 2021). Additionally, the challenging psychedelic experiences may still hold value and be rated among the most personally meaningful in participants (Griffiths, Richards, Johnson, McCann, & Jesse, 2008).
Similar to psychedelics, MDMA has been noted to produce dissociative or altered states of consciousness, although not as reliably as large doses of psychedelics (Barrett & Griffiths, 2018; Griffiths, Richards, McCann, & Jesse, 2006; Grob & Grigsby, 2021, p. 250). The mystical experience has been demonstrated to correlate significantly with positive therapeutic outcomes in psilocybin trials. In contrast, this correlation hasn't been shown with MDMA (Grob & Grigsby, 2021). Interestingly, results of a placebo-controlled within-subject study suggest that, unlike psychedelics, the dissociative state of MDMA is not explicitly associated with 5-HT2A receptor activity (Puxty et al., 2017). The therapeutic utility of MDMA could be more related to the prosocial and emotional effects of the drug as opposed to the drastic conscious altering states and reduced ego integrity resulting in profound new insights induced by psychedelics.
Neurobiological effects of MDMA and psychedelics
Neural correlates
Several studies have investigated the neural correlates of the subjective effects of MDMA to expand our understanding of the potential neurobiological mechanisms. MDMA has shown changes in activity in brain regions involved in the amygdala, hippocampus (HPC), ventral striatum, midline cortical regions, posterior cingulate cortex, ventromedial prefrontal cortex (vmPFC), and the medial temporal lobe (Bedi, Phan, Angstadt, & de Wit, 2009; Carhart-Harris et al., 2015). Psychedelics have a more profound effect on global brain function and increase the resting state functional connectivity (RSFC) between normally segregated neural networks while decreasing within-network connectivity in the default mode network (DMN), resulting in a net increase in brain entropy (Carhart-Harris et al., 2014; Holas & Kamińska, 2023; Roseman et al., 2014).
MDMA's effects on medial temporal lobe regions
The amygdala, part of the limbic system, is crucial in emotional regulation, reacting to fear, anger, and pleasure (Roozendaal, McEwen, & Chattarji, 2009; Roozendaal & McGaugh, 2011). It interacts with regions like the hippocampus and mPFC for fear processing and emotional memory and is involved in social behavior, decision-making, and reward processing (Baxter & Murray, 2002; Gallagher & Chiba, 1996; Hermans et al., 2014; Phelps & LeDoux, 2005).
A pivotal study by Bedi et al. (2009) revealed that MDMA reduces amygdala response to angry faces and increases ventral striatum activity to happy faces, suggesting MDMA affects emotional processing. Singleton et al. (2023) found that MDMA-assisted therapy (MDMA-AT) for PTSD patients enhances amygdala-hippocampus connectivity, particularly during memory recall, indicating potential benefits for trauma recovery. This RSFC finding was replicated in a prior study by Carhart-Harris et al., 2015 in mentally healthy individuals. In the study, the RSFC changes showed a trend-level correlation with the intensity of global subjective experiences rated by participants, although they did not reach statistical significance. On the other hand, a significant positive correlation was found between the intensity of global subjective effects of MDMA and the magnitude of decrease in cerebral blood flow (CBF) in relevant areas involved in affective processing, such as the right amygdala (p = 0.002) and right hippocampus (p = 0.004). These studies highlight MDMA's influence on the brain regions related to emotional memory processing and its potential therapeutic applications.
Default mode network: psychedelics vs. MDMA
The DMN is one of many resting-state networks (RSN), which comprises spatially, anatomically distinct but temporally co-activated and functionally connected midline brain structures (Andrews-Hanna, Smallwood, & Spreng, 2014; Gattuso et al., 2022; Raichle et al., 2001). DMN activity increases during non-task-oriented cognition and involves mind-wandering, introspection, self-referential processing, and autobiographical thinking. The DMN consists of a few brain regions, including the medial prefrontal cortex (mPFC), precuneus, and posterior cingulate cortex (PCC). Together, they support various internal mental activities and are crucial for introspective processes, ego integrity, and constructing personal narratives (Raichle et al., 2001; Roseman et al., 2014). In contrast, during external task-oriented cognition, a collection of functionally connected brain regions become active, collectively called task-positive networks (TPN). The TPN includes the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and intraparietal sulcus (IPS). In ordinary consciousness, the activity of the DMN and TPNs are anticorrelated or inversely related, i.e., during external task-oriented cognition, the TPN is more engaged while DMN activity is reduced and vice versa (Fox et al., 2005; Roseman et al., 2014).
Both psilocybin and MDMA have been shown to decrease the intra-DMN RSFC between the mPFC and PCC (Carhart-Harris et al., 2015; Gattuso et al., 2022; Grob & Grigsby, 2021, p. 237; Roseman et al., 2014). More generally, psychedelics have been shown to have a more profound effect on global brain function by increasing between-RSN connectivity (decreased segregation) compared to MDMA (Gattuso et al., 2022; Roseman et al., 2014). These findings could explain why classic psychedelics have a more extensive effect on consciousness and their propensity for mystical experiences. The anti-correlation between the DMN and TPN also becomes less distinct and, together with the internal destabilization of RSFC within the DMN, has been interpreted as a potential neural correlate for the subjective experience of unitive consciousness, often described as a blurring of boundaries between the subjective-internal and objective-external (Carhart-Harris et al., 2012; Richards & Barnard, 2016; Roseman et al., 2014).
The decreased segregation of the functional organization of the brain observed in psychedelic states has been implicated as the basis for the entropic brain hypothesis (Carhart-Harris, 2018; Carhart-Harris et al., 2014). The hypothesis proposes that brain criticality, in which neuronal systems operate at a critical transition between order and randomness, enables the brain to be more sensitive to information processing of internal and external stimuli and hence be implicated in the profound effect “set” (internal) and “setting” (external) has in psychedelic states (Carhart-Harris, 2018). The DMN is also relevant to conditions such as depression, characterized by hyperactivity in the mPFC (Carhart-Harris, 2019; Gattuso et al., 2022; Morris, 2008; Nichols, 2016). Moreover, depressive symptoms appear to be inversely correlated with the degree of 5-HT1A receptor stimulation in the mPFC (Carhart-Harris, 2019; Gattuso et al., 2022).
Neuroplasticity
BDNF is a growth factor involved with neuroplasticity. Disordered BDNF signaling is suggested as part of the pathophysiology of some psychological disorders. For example, abnormal BDNF signaling during the formation of new fear memory associations has been implicated as part of the pathology of PTSD (Sottile & Vida, 2022). Disruptions in neuroplastic processes might affect fear learning extinction and memory reconsolidation necessary for altering a conditioned response (Sottile & Vida, 2022). Furthermore, evidence suggests that atrophy of neurons in the prefrontal cortex (PFC) is observed in conditions such as depression (Ly et al., 2018). Thus, counteracting these structural changes with substances that promote dendritic spine growth, dendritic and axonal branching, and synapse formation are of significant clinical interest to study.
MDMA, psychedelics, and ketamine have plausible therapeutic mechanisms related to increasing neuro-metaplasticity in the brain via neurotrophic signaling mediated by increased BDNF secondary to 5-HT2A signaling (Aleksandrova & Phillips, 2021; de Vos, Mason, & Kuypers, 2021; Holas & Kamińska, 2023). Additionally, the activation of mammalian target of rapamycin (mTOR) may also be involved, specifically by classic psychedelics and ketamine (Aleksandrova & Phillips, 2021; Holas & Kamińska, 2023; Inserra, De Gregorio, & Gobbi, 2021; Ly et al., 2018). At least part of MDMA's structural plasticity is related to 5-HT2A receptor activation, as the administration of ketanserin, a 5-HT2A receptor antagonist, blocked the effects of neuritogenesis and spinogenesis (Ly et al., 2018).
Neuroplasticity is also implicated in learning as it requires modification of neuronal connections (Galván, 2010). Nardou et al. (2019, 2023) showed that psychedelics and MDMA reopen the social reward learning critical period in mice. Oxytocin-mediated metaplastic changes seem to be involved in MDMA-induced reopening of the social reward learning critical period (Nardou et al., 2019). On the other hand, 5-HT2A receptor signaling appears to be the primary dependent mechanism by which psychedelics reopen social reward learning. Nardou et al. (2023) evidenced this by demonstrating ketanserin blocking the reopening of the social reward learning critical period in mice given LSD or psilocybin but not for those given MDMA.
A more recent study in mice suggests that plasticity mediated by psychedelics is partly due to binding allosterically to the BDNF receptor, neurotrophic receptor tyrosine kinase (TrkB), modulating the endogenous effects of extracellular BDNF independent of 5-HT2A receptor activation (Moliner et al., 2023). In contrast, Vargas et al. (2023) found that psychedelics may promote plasticity via the activation of intracellular 5-HT2A receptors in a way that endogenous serotonin does not. Ultimately, more studies need to be conducted to elucidate further the therapeutic actions and underlying mechanisms of neuroplasticity by psychedelics and MDMA.
Synergistic potential of meditation with psychedelics or MDMA therapy
While meditation is an ancient practice rooted primarily in Eastern traditions such as Hinduism and Buddhism, its incorporation into Western psychotherapy is relatively recent and informed by research (Simonds, 2023). There has been an exponential increase in recent decades exploring the science of meditation. In 1990, there were fewer than 100 studies, but by 2015, there were over 1,000, with a continued increase today (Goleman & Davidson, 2017, p. 14). Evidence suggests that various forms of meditation have implications for relieving symptoms of depression, anxiety, and PTSD, as well as improving resilience to stress, emotional regulation, and promoting well-being (Kim et al., 2022). The underlying mechanism of these clinical benefits is of significant interest. There is evidence of overlapping phenomenological, psychological, and neurobiological effects produced by meditation, MDMA, and psychedelics, which has led to several review papers suggesting a potential synergy (Chambers et al., 2023; Eleftheriou & Thomas, 2021; Holas & Kamińska, 2023; Payne et al., 2021; Simonds, 2023).
Meditation approaches
Important distinctions exist between the various forms of meditation, such as loving-kindness meditation (LKM) and mindfulness meditation (MM), since each form varies in phenomenology and technique (Goleman & Davidson, 2017, p. 68, 115). One study trained several hundred participants in MM and LKM over 11 months vs. a control group without training and found that mindfulness-based practices increased somatic awareness and meta-awareness and decreased mind wandering (Goleman & Davidson, 2017, p. 115; Kok & Singer, 2017). In contrast, LKM increased caring attitudes about others. Thus, the specific type of meditation should inform the problem or symptom being addressed, how studies are designed, and how results are interpreted (Goleman & Davidson, 2017, pp. 68–69, 115).
Mindfulness is a form of meta-awareness practice anchoring one's mind in the present moment through concentration, observing when the mind has wandered (Goleman & Davidson, 2017, pp. 74–75; Millière, Carhart-Harris, Roseman, Trautwein, & Berkovich-Ohana, 2018). There are two main approaches to mindfulness practice. The first is through focused attention (FA), akin to shining an attentional spotlight (Goleman & Davidson, 2017, pp. 74–75; Millière et al., 2018). Individuals concentrate on a particular somatosensory sensation, commonly the breath, and return to it repetitively when noticing the mind has wandered. The second is open monitoring (OM), likened to shining an attentional flood light. A practitioner opens awareness to the entirety of their experience, observing all phenomena arising in consciousness, including thoughts, feelings, and sensations (Goleman & Davidson, 2017, pp. 74–75; Millière et al., 2018). Both techniques aim for non-judgemental reactions or attachments. One study suggests a gradual progression from training in FA first and then to OM improves well-being to a greater degree than either alone (Chambers et al., 2023; Cullen et al., 2021).
LKM is designed to cultivate feelings of unconditional kindness and compassion toward oneself or others (Shonin, Van Gordon, Compare, Zangeneh, & Griffiths, 2015). It involves the silent repetition of phrases expressing wishes for well-being, happiness, and freedom from hate or suffering. MBIs and LKM are both associated with psychological benefits and promoting well-being (Kim et al., 2022; Shonin et al., 2015). As evidenced by overlapping psychological and neurobiological effects, they may have the potential to synergize with psychedelic therapy and MDMA-AT in unique ways.
Overlap in psychological effects
Prosociality
MDMA and psychedelics could enhance well-being by fostering prosocial attitudes, empathy, and compassion for self and others (Chambers et al., 2023; Payne et al., 2021). Psychedelics may do so by modifying self-narratives or perspectives, with the potential to generate newly embodied insights, a positive mood, and a profound sense of unity or interconnectedness. In contrast, MDMA has more direct effects on emotional circuits, reducing fear and psychological defenses (Feduccia & Mithoefer, 2018; Grob & Grigsby, 2021; Mithoefer et al., 2016; Sessa et al., 2019). As opposed to the more acute effects of psychedelics and MDMA, MBIs gradually shift self-perception and self-awareness, and those incorporating LKM result in enhanced empathy, compassion, and social connectedness (Goleman & Davidson, 2017; Holas & Kamińska, 2023). Eastern traditions, such as Vipassana, emphasize a combined meditative practice that includes self-compassion and loving-kindness. Mindfulness without compassion can paradoxically lead to maladaptive coping mechanisms such as repression (Payne et al., 2021; Shapiro, Carlson, Astin, & Freedman, 2006).
Psychological flexibility
Psychological flexibility induced by psychedelics and MDMA has been proposed as one significant mediator of their beneficial effects. Both can increase the personality trait of Openness and generate insights into personal values (Mark et al., 2017; Payne et al., 2021). Psychedelics allow an individual to deconstruct rigid thought patterns and enhance emotional receptivity (Davis, Barrett, & Griffiths, 2020; Kuypers, 2018). By reducing fear and defensiveness, MDMA facilitates acceptance and less resistance to approaching difficult or traumatic emotional memories (Feduccia & Mithoefer, 2018; Sessa et al., 2019).
The psychological flexibility and openness offered by MBIs are inherent in its methods. A primary aim of MBIs is to generate present-moment awareness and foster acceptance of whatever arises in a non-judgmental way (Goleman & Davidson, 2017; Kok & Singer, 2017). Mindfulness practices, therefore, allow an individual to navigate challenging emotions and reduce fear and avoidance while examining rigid thought patterns. In this way, MDMA, psychedelics, and MBIs can increase adaptability and value-based behavior in the face of challenging thoughts or emotions, and MBIs could potentially synergize with either substance to sustain these effects.
Decentering
Decentering is the ability to objectively view the contents of consciousness, including thoughts, feelings, perceptions, and emotions, without being heavily identified with them. Research suggests MM and psychedelics can promote decentering (Chambers et al., 2023; Eleftheriou & Thomas, 2021; Holas & Kamińska, 2023). MM practices intentionally invite the individual to remain present, noting any arising phenomena without attachment, avoidance, or judgment (Goleman & Davidson, 2017). This promotes a decentering capacity and changes how one relates to one's thoughts and emotions. Likewise, psychedelics may induce this phenomenon through profound shifts in consciousness in which the usual self or ego constructs are diminished, resulting in a novel perspective from a more distant, objective stance (Chambers et al., 2023; Eleftheriou & Thomas, 2021; Holas & Kamińska, 2023). Given the decentering capacities of MM and psychedelics, research using protocols combining their use to address psychopathology could be an area of exploration. Furthermore, MM training before and utilized during the MDMA or psychedelic dosing session might refine decentering capacities to minimize challenging experiences encountered in the form of unpleasant thoughts, emotions, or memories by reducing avoidance or reactivity to them during the experience.
Neurobiological overlap
The overlap in neural activity between meditation and MDMA involves key brain regions such as the amygdala, HPC, and the connectivity between the vmPFC and the PCC (Carhart-Harris et al., 2015; Grob & Grigsby, 2021, p. 237; Kral et al., 2019; Zsadanyi, Kurth, & Luders, 2021). Both meditation and MDMA use can lead to reduced reactivity by the amygdala, which is associated with emotional processing, potentially explaining the subjective correlation of reducing fear and anxiety. Effects on HPC activity may affect how emotional memories are processed and recalled. Similarly, LKM has shown altered amygdala size in expert meditators and heightened activity on fMRI when instructed to initiate LKM during brain scans. The vmPFC-PCC connectivity, as part of the DMN, is reduced by psychedelics, suggesting a shift away from self-referential thought processes and a reduction in egocentric behavior (Grob & Grigsby, 2021). This overlap extends to meditation; DMN activity is reduced during FA, and experienced meditators appear to have DMN activity decreased during resting states compared to meditation-naive (Brewer et al., 2011; Giuseppe Pagnoni, 2012; Holas & Kamińska, 2023). Decreased vmPFC-PCC has also been observed under MDMA's effects, but global functional connectivity remains more segregated compared to psychedelics (Carhart-Harris et al., 2015; Grob & Grigsby, 2021, p. 237; Roseman et al., 2014). Psychedelics produce much more increased connectivity between RSNs, potentially explaining the significant blurring of boundaries between internal and external stimuli (Carhart-Harris, 2018; Roseman et al., 2014). Significant reductions in DMN activity and connectivity correlate with the phenomenologic experience of ego dissolution and unity with one's environment (Carhart-Harris, Muthukumaraswamy, et al., 2016; Millière et al., 2018). This is a common phenomenon described in deep meditative states and psychedelic experiences (Millière et al., 2018).
Neuroplasticity is suggested to play a significant role in the therapeutic effects of psychedelics, MDMA, and meditation, ultimately promoting lasting changes in brain structure and function (Aleksandrova & Phillips, 2021; de Vos et al., 2021; Felsch & Kuypers, 2022; Inserra et al., 2021; Kral et al., 2019; Ly et al., 2018; Moliner et al., 2023; Vargas et al., 2023). As previously discussed, psychedelics and MDMA may promote BDNF-mediated neuroplasticity, resulting in the growth of dendrites and synapse formation, which has been suggested to enhance cognitive flexibility, emotional resilience, memory reconsolidation, and psychological well-being. Long-term meditation promotes neuroplasticity by strengthening neural pathways associated with attention, emotional regulation, and self-awareness (Goleman & Davidson, 2017). Perhaps neuroplasticity is relevant to the potential synergy between meditation and psychedelics in mental health treatment and personal growth.
Potential synergy during the arc of therapy
The synergy between meditation (MBIs and LKM) and psychedelics or MDMA could plausibly be bidirectional. Meditation-based frameworks could be helpful for different reasons in each phase of the arc (preparation, dosing, integration) of psychedelic-assisted psychotherapy (PAPT) and MDMA-AT (Payne et al., 2021; Simonds, 2023). Likewise, psychedelics or MDMA could produce acutely altered states, which increase the propensity of novice meditators to recognize and embody the valuable qualities of the meditative practice in ways that might not have been readily apparent without years of practice. This is the basis for the compass and vehicle analogy proposed by Payne et al. (2021). They further reported studies demonstrating that short and long-term mindfulness capacities increase following a single use, particularly with 5-MeO-DMT, psilocybin, and ayahuasca (Madsen et al., 2020; Mian, Altman, & Earleywine, 2020; Murphy-Beiner & Soar, 2020; Payne et al., 2021; Sampedro et al., 2017; Soler et al., 2016; Uthaug et al., 2019). The evidence suggests meditation could help stabilize the insights gleaned from the dosing session and aid in integration into day-to-day life, while the altered states induced by psychedelics could encourage one's curiosity and openness to adopt and maintain a meditative practice (Grob & Grigsby, 2021, p. 399; Payne et al., 2021; Smigielski et al., 2019). Smigielski et al. (2019) demonstrated that psilocybin administered with meditation in a group retreat setting could reduce the anxiety associated with ego dissolution often experienced during the drug's peak effects. Compared to a control group, meditation also amplified the intensity of blissful, spiritual, and unitive states, enhancing the overall positive experience (Payne et al., 2021; Smigielski et al., 2019). A systematic review of psilocybin-assisted MBI's proposed benefit in those with social anxiety disorder through alteration in cognitive processes such as attentional and emotional regulation related to perceived threat (Felsch & Kuypers, 2022). This finding suggests a potential utility of MBIs in the preparation and dosing phase of PAPT by offering structured approaches that influence the “Set” of the individual during the peak experience to maximize therapeutic potential and minimize harm. The brain entropic theory supports the notion that psychedelics might make individuals more sensitive to internal and external stimuli, possibly explaining the profound effect “Set” and “Setting” have on the experience (Carhart-Harris, 2018). Meditation training, therefore, could be a practical way to prime the mindset for the journey in its totality.
Furthermore, LKM might be a valuable adjunct to MDMA-AT, particularly in the integration phase with individuals being treated for PTSD. A phase 3 randomized, placebo-controlled trial studying MDMA-AT for moderate to severe PTSD revealed significant reductions in symptoms and more than double the remission rate compared to placebo (Mitchell et al., 2023). Another phase 3 trial had similar findings (Mitchell et al., 2021). One study looked at the effect a 12-week LKM training had on veterans with PTSD and found that symptoms of PTSD and depression had lessened (Goleman & Davidson, 2017, p. 201; Kearney et al., 2013). Another study found a similar significant reduction in PTSD symptoms in veterans utilizing LKM vs. an active control group (Lang et al., 2019). Combining LKM and MDMA-AT in treatment protocols, which are both capable of increasing prosociality, empathy, and self-compassion while reducing fear and PTSD symptoms, warrants further research.
Altered states vs. altered traits with meditation and hallucinogens
Meditation and psychedelic therapies can both induce altered states and mystical experiences that can lead to profound insights and experiences. Davidson and Goleman highlight in their book, Altered Traits: Science Reveals How Meditation Changes Your Mind, Brain, and Body, that temporarily altered states from meditation can eventually become sustained shifts in personal transformation if repeatedly experienced over time (Cásedas, 2021; Goleman & Davidson, 2017). They coined this permanent, more stable shift as ‘altered traits’ and emphasized that repeated practice is likely needed to maintain these changes. This concept parallels psychedelic therapy, where a temporarily altered state can lead to significant insights and emotional breakthroughs and is followed by integration. The integration process following the MDMA or psychedelic experience, similar to a disciplined practice in meditation, aims to create long-term personal transformation. In either case, these lasting changes are proposed to be mediated by neuroplasticity (Aleksandrova & Phillips, 2021; Cásedas, 2021; de Vos et al., 2021; Goleman & Davidson, 2017, pp. 41–58; Inserra et al., 2021; Ly et al., 2018; Moliner et al., 2023; Vargas et al., 2023). However, there's a paradox in compulsively pursuing these altered states as the sole objective. Unrecognized attachment to them can contradict the underlying goals of personal growth, well-being, and healing, which include enhanced meta-awareness, non-attachment, acceptance, compassion, and empathy. A balance between experiencing altered states of consciousness and integrating to promote altered traits of consciousness seems necessary for genuine long-term effects.
In summary, the sole aim of meditation is not to produce mystical states of consciousness; instead, it is to appreciate the true nature of everyday ordinary consciousness with present awareness or observation and stabilize compassionate attitudes and mindfulness capacities. While NOSC is a possible outcome of deep meditative states, whether it is a prerequisite for insight remains debatable. Disciplined and repetitive practice is likely needed for lasting change. On the other hand, the NOSC produced by sufficient doses of psychedelics and MDMA is less avoidable due to the direct effects of the drug. The magnitude of these direct effects also presents challenges with blinding in clinical trials. While NOSC can provide valuable insights and intense experiences, integration is important for genuine, sustained well-being in daily life. The principles of MM and LKM practices offer a potential framework for integration, especially during the reopening of the social reward learning critical period shortly after a psychedelic or MDMA experience.
Conclusion
Meditation practices share commonalities with altered states produced by MDMA and psychedelics in promoting well-being, compassion, empathy, and a sense of connectedness. This overlap suggests that combining LKM and MM with MDMA-AT or PAPT could synergize to enhance therapeutic outcomes in unique ways. Each offers a potential pathway for facilitating long-term psychological flexibility, emotional and attentional regulation, and a sustained sense of well-being. More research combining these practices could reveal novel methods for addressing mental health conditions and personal growth. The therapeutic mechanisms of non-ordinary states of consciousness induced by MDMA and psychedelics require continued exploration, offering exciting possibilities for the future of mental health treatment and our understanding of consciousness.
Funding sources
None.
Authors' contributions
This paper was written solely by the author, Dr. Jacob T. Dines.
Conflicts of interest
The author declares no conflicts of interest related to this manuscript.
Ethical statement
This review did not involve the experimentation of any animal or human subjects. The author affirms no conflicts of interest related to the content of this manuscript. No external funding was received. The author has adhered to the Journal of Psychedelic Studies' ethical standards regarding publication ethics, including transparency, accuracy, and proper citation of all sources.
References
Aleksandrova, L. R., & Phillips, A. G. (2021). Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends in Pharmacological Sciences, 42(11), 929–942. https://doi.org/10.1016/j.tips.2021.08.003.
Andrews-Hanna, J. R., Smallwood, J., & Spreng, R. N. (2014). The default network and self-generated thought: Component processes, dynamic control, and clinical relevance. Annals of the New York Academy of Sciences, 1316(1), 29–52. https://doi.org/10.1111/nyas.12360.
Barrett, F. S., & Griffiths, R. R. (2018). Classic hallucinogens and mystical experiences: Phenomenology and neural correlates. Current Topics in Behavioral Neurosciences, 36, 393–430. https://doi.org/10.1007/7854_2017_474.
Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2017). Neuroticism is associated with challenging experiences with psilocybin mushrooms. Personality and Individual Differences, 117, 155–160. https://doi.org/10.1016/j.paid.2017.06.004.
Baxter, M. G., & Murray, E. A. (2002). The amygdala and reward. Nature Reviews Neuroscience, 3(7), 563–573. https://doi.org/10.1038/nrn875.
Bedi, G., Phan, K. L., Angstadt, M., & de Wit, H. (2009). Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology, 207(1), 73–83. https://doi.org/10.1007/s00213-009-1635-z.
Brewer, J. A., Worhunsky, P. D., Gray, J. R., Tang, Y., Weber, J., & Kober, H. (2011). Meditation experience is associated with differences in default mode network activity and connectivity. Proceedings of the National Academy of Sciences, 108(50), 20254–20259. https://doi.org/10.1073/pnas.1112029108.
Carhart-Harris, R. L. (2018). The entropic brain - revisited. Neuropharmacology, 142, 167–178. https://doi.org/10.1016/j.neuropharm.2018.03.010.
Carhart-Harris, R. L. (2019). How do psychedelics work? Current Opinion in Psychiatry, 32(1), 16–21.
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., … Nutt, D. J. (2016). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychological Medicine, 46(7), 1379–1390. https://doi.org/10.1017/S0033291715002901.
Carhart-Harris, R. L., Leech, R., Erritzoe, D., Williams, T. M., Stone, J. M., Evans, J., … Nutt, D. J. (2012). Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophrenia Bulletin, 39(6), 1343–1351. https://doi.org/10.1093/schbul/sbs117.
Carhart-Harris, R., Leech, R., Hellyer, P., Shanahan, M., Feilding, A., Tagliazucchi, E., … Nutt, D. (2014). The entropic brain: A theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 8. Retrieved from https://www.frontiersin.org/articles/10.3389/fnhum.2014.00020.
Carhart-Harris, R., Leech, R., Hellyer, P., Shanahan, M., Feilding, A., Tagliazucchi, E., ... Nutt, D. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences, 113(17), 4853–4858. https://doi.org/10.1073/pnas.1518377113.
Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … Nutt, D. J. (2015). The effects of acutely administered 3,4-methylenedioxymethamphetamine on spontaneous brain function in healthy volunteers measured with arterial spin labeling and blood oxygen Level–Dependent resting state functional connectivity. Biological Psychiatry, 78(8), 554–562. https://doi.org/10.1016/j.biopsych.2013.12.015.
Cásedas, L. (2021). Daniel goleman and richard J. davidson: Altered traits: Science reveals how meditation changes your mind, brain, and body. Avery, New York, NY, 2017, 336 pp [book review]. Mindfulness. https://doi.org/10.1007/s12671-021-01650-4.
Chambers, R., Stoliker, D., & Simonsson, O. (2023). Psychedelic-assisted psychotherapy and mindfulness-based cognitive therapy: Potential synergies. Mindfulness, 14(9), 2111–2123. https://doi.org/10.1007/s12671-023-02206-4.
Cullen, B., Eichel, K., Lindahl, J. R., Rahrig, H., Kini, N., Flahive, J., & Britton, W. B. (2021). The contributions of focused attention and open monitoring in mindfulness-based cognitive therapy for affective disturbances: A 3-armed randomized dismantling trial. Plos One, 16(1), e0244838. https://doi.org/10.1371/journal.pone.0244838.
Davis, A. K., Barrett, F. S., & Griffiths, R. R. (2020). Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioral Science, 15, 39–45. https://doi.org/10.1016/j.jcbs.2019.11.004.
de Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. (2021). Psychedelics and neuroplasticity: A systematic review unraveling the biological underpinnings of psychedelics. Frontiers in Psychiatry, 12, 724606. https://doi.org/10.3389/fpsyt.2021.724606.
Dyck, E., & Elcock, C. (2020). Reframing bummer trips: Scientific and cultural explanations to adverse reactions to psychedelic drug use. The Social History of Alcohol and Drugs, 34(2), 271–296. https://doi.org/10.1086/707512.
Eleftheriou, M. E., & Thomas, E. (2021). Examining the potential synergistic effects between mindfulness training and psychedelic-assisted therapy. Frontiers in Psychiatry, 12, 788107. Retrieved from https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.707057.
Feduccia, A. A., & Mithoefer, M. C. (2018). MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Progress in Neuro-Psychopharmacology & Biological Psychiatry, 84(Pt A), 221–228. https://doi.org/10.1016/j.pnpbp.2018.03.003.
Felsch, C. L., & Kuypers, K. P. C. (2022). Don't be afraid, try to meditate- potential effects on neural activity and connectivity of psilocybin-assisted mindfulness-based intervention for social anxiety disorder: A systematic review. Neuroscience and Biobehavioral Reviews, 139, 104724. https://doi.org/10.1016/j.neubiorev.2022.104724.
Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences, 102(27), 9673–9678. https://doi.org/10.1073/pnas.0504136102.
Gallagher, M., & Chiba, A. A. (1996). The amygdala and emotion. Current Opinion in Neurobiology, 6(2), 221–227. https://doi.org/10.1016/S0959-4388(96)80076-6.
Galván, A. (2010). Neural plasticity of development and learning. Human Brain Mapping, 31(6), 879–890. https://doi.org/10.1002/hbm.21029.
Gashi, L., Sandberg, S., & Pedersen, W. (2021). Making “bad trips” good: How users of psychedelics narratively transform challenging trips into valuable experiences. International Journal of Drug Policy, 87, 102997. https://doi.org/10.1016/j.drugpo.2020.102997.
Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., … Sarris, J. (2022). Default mode network modulation by psychedelics: A systematic review. International Journal of Neuropsychopharmacology, 26(3), 155–188. https://doi.org/10.1093/ijnp/pyac074.
Giuseppe Pagnoni (2012). Dynamical properties of BOLD activity from the ventral posteromedial cortex associated with meditation and attentional skills. The Journal of Neuroscience, 32(15), 5242–5249. https://doi.org/10.1523/JNEUROSCI.4135-11.2012.
Goleman, D., & Davidson, R. J. (2017). Altered traits: Science reveals how meditation changes your mind, brain, and body avery. Retrieved from https://books.google.com/books?id=AdF0nQAACAAJ.
Green, A. R., Mechan, A. O., Elliott, J. M., O'Shea, E., & Colado, M. I. (2003). The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacological Reviews, 55(3), 463–508. https://doi.org/10.1124/pr.55.3.3.
Griffiths, R., Richards, W., Johnson, M., McCann, U., & Jesse, R. (2008). Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of Psychopharmacology (Oxford, England), 22(6), 621–632. https://doi.org/10.1177/0269881108094300.
Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268–292. https://doi.org/10.1007/s00213-006-0457-5.
Grob, C. S., & Grigsby, J. (2021). Handbook of medical hallucinogens. New York: The Guilford Press.
Hermans, E. J., Battaglia, F. P., Atsak, P., de Voogd, L. D., Fernández, G., & Roozendaal, B. (2014). How the amygdala affects emotional memory by altering brain network properties. Neurobiology of Learning and Memory, 112, 2–16. https://doi.org/10.1016/j.nlm.2014.02.005.
Holas, P., & Kamińska, J. (2023). Mindfulness meditation and psychedelics: Potential synergies and commonalities. Pharmacological Reports, 75(6), 1398–1409. https://doi.org/10.1007/s43440-023-00551-8.
Holze, F., Vizeli, P., Müller, F., Ley, L., Duerig, R., Varghese, N., … Liechti, M. E. (2020). Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 45(3), 462–471. https://doi.org/10.1038/s41386-019-0569-3.
Hysek, C. M., Domes, G., & Liechti, M. E. (2012). MDMA enhances “mind reading” of positive emotions and impairs “mind reading” of negative emotions. Psychopharmacology, 222(2), 293–302. https://doi.org/10.1007/s00213-012-2645-9.
Hysek, C. M., Schmid, Y., Simmler, L. D., Domes, G., Heinrichs, M., Eisenegger, C., … Liechti, M. E. (2013). MDMA enhances emotional empathy and prosocial behavior. Social Cognitive and Affective Neuroscience, 9(11), 1645–1652. https://doi.org/10.1093/scan/nst161.
Inserra, A., De Gregorio, D., & Gobbi, G. (2021). Psychedelics in psychiatry: Neuroplastic, immunomodulatory, and neurotransmitter mechanisms. Pharmacological Reviews, 73(1), 202–277. https://doi.org/10.1124/pharmrev.120.000056.
Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: Guidelines for safety. Journal of Psychopharmacology, 22(6), 603–620. https://doi.org/10.1177/0269881108093587.
Kearney, D. J., Malte, C. A., McManus, C., Martinez, M. E., Felleman, B., & Simpson, T. L. (2013). Loving-kindness meditation for posttraumatic stress disorder: A pilot study. Journal of Traumatic Stress, 26(4), 426–434. https://doi.org/10.1002/jts.21832.
Kim, D., Hong, S., Jang, S., Park, S., Noh, J., Seok, J., … Lee, E. (2022). Systematic review for the medical applications of meditation in randomized controlled trials. International Journal of Environmental Research and Public Health, 19(3). https://doi.org/10.3390/ijerph19031244.
Ko, K., Knight, G., Rucker, J. J., & Cleare, A. J. (2022). Psychedelics, mystical experience, and therapeutic efficacy: A systematic review. Frontiers in Psychiatry, 13. Retrieved from https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.917199.
Kok, B. E., & Singer, T. (2017). Phenomenological fingerprints of four meditations: Differential state changes in affect, mind-wandering, meta-cognition, and interoception before and after daily practice across 9 months of training. Mindfulness, 8(1), 218–231. https://doi.org/10.1007/s12671-016-0594-9.
Kral, T. R. A., Imhoff-Smith, T., Dean, D. C.,III, Grupe, D., Adluru, N., Patsenko, E., … Davidson, R. J. (2019). Mindfulness-based stress reduction-related changes in posterior cingulate resting brain connectivity. Social Cognitive and Affective Neuroscience, 14(7), 777–787. https://doi.org/10.1093/scan/nsz050.
Kuypers, K. P. C. (2018). Out of the box: A psychedelic model to study the creative mind. Medical Hypotheses, 115, 13–16. https://doi.org/10.1016/j.mehy.2018.03.010.
Lang, A. J., Malaktaris, A. L., Casmar, P., Baca, S. A., Golshan, S., Harrison, T., & Negi, L. (2019). Compassion meditation for posttraumatic stress disorder in veterans: A randomized proof of concept study. Journal of Traumatic Stress, 32(2), 299–309. https://doi.org/10.1002/jts.22397.
Lebedev, A. V., Kaelen, M., Lövdén, M., Nilsson, J., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2016). LSD-induced entropic brain activity predicts subsequent personality change. Human Brain Mapping, 37(9), 3203–3213. https://doi.org/10.1002/hbm.23234.
Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., … Olson, D. E. (2018). Psychedelics promote structural and functional neural plasticity. Cell Reports, 23(11), 3170–3182. https://doi.org/10.1016/j.celrep.2018.05.022.
MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of Psychopharmacology (Oxford, England), 25(11), 1453–1461. https://doi.org/10.1177/0269881111420188.
Madsen, M. K., Fisher, P. M., Stenbæk, D. S., Kristiansen, S., Burmester, D., Lehel, S., … Knudsen, G. M. (2020). A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 33, 71–80. https://doi.org/10.1016/j.euroneuro.2020.02.001.
Mark, T. W., Michael, C. M., Ann, T. M., Rebecca, K. M., Jerome, L., Yazar-Klosinski, B., & Doblin, R. (2017). Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. J Psychopharmacol, 31(8), 967–974. https://doi.org/10.1177/0269881117711712.
Mian, M. N., Altman, B. R., & Earleywine, M. (2020). Ayahuasca's antidepressant effects covary with behavioral activation as well as mindfulness. Journal of Psychoactive Drugs, 52(2), 130–137. https://doi.org/10.1080/02791072.2019.1674428.
Millière, R., Carhart-Harris, R., Roseman, L., Trautwein, F., & Berkovich-Ohana, A. (2018). Psychedelics, meditation, and self-consciousness. Frontiers in Psychology, 9. Retrieved from https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2018.01475.
Mitchell, J. M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K., … Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine, 27(6), 1025–1033. https://doi.org/10.1038/s41591-021-01336-3.
Mitchell, J. M., Ot’alora G., M., van der Kolk, B., Shannon, S., Bogenschutz, M., Gelfand, Y., … Yazar-Klosinski, B. (2023). MDMA-assisted therapy for moderate to severe PTSD: A randomized, placebo-controlled phase 3 trial. Nature Medicine, 29(10), 2473–2480. https://doi.org/10.1038/s41591-023-02565-4.
Mithoefer, M. C., Grob, C. S., & Brewerton, T. D. (2016). Novel psychopharmacological therapies for psychiatric disorders: Psilocybin and MDMA. The Lancet Psychiatry, 3(5), 481–488. https://doi.org/10.1016/S2215-0366(15)00576-3.
Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V., Biojone, C., Enkavi, G., … Castrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature Neuroscience, 26(6), 1032–1041. https://doi.org/10.1038/s41593-023-01316-5.
Morris, K. (2008). Research on psychedelics moves into the mainstream. Lancet (London, England), 371(9623), 1491–1492. https://doi.org/10.1016/s0140-6736(08)60638-8.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca's 'afterglow': Improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 237(4), 1161–1169. https://doi.org/10.1007/s00213-019-05445-3.
Nardou, R., Lewis, E. M., Rothhaas, R., Xu, R., Yang, A., Boyden, E., & Dölen, G. (2019). Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature, 569(7754), 116–120. https://doi.org/10.1038/s41586-019-1075-9.
Nardou, R., Sawyer, E., Song, Y. J., Wilkinson, M., Padovan-Hernandez, Y., de Deus, J. L., … Dölen, G. (2023). Psychedelics reopen the social reward learning critical period. Nature, 618(7966), 790–798. https://doi.org/10.1038/s41586-023-06204-3.
Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews, 68(2), 264–355.
Nichols, D. E. (2022). Entactogens: How the name for a novel class of psychoactive agents originated. Frontiers in Psychiatry, 13, 863088. https://doi.org/10.3389/fpsyt.2022.863088.
Parrott, A. C. (2009). Cortisol and 3,4-methylenedioxymethamphetamine: Neurohormonal aspects of bioenergetic stress in ecstasy users. Neuropsychobiology, 60(3–4), 148–158. https://doi.org/10.1159/000253551.
Payne, J. E., Chambers, R., & Liknaitzky, P. (2021). Combining psychedelic and mindfulness interventions: Synergies to inform clinical practice. ACS Pharmacology & Translational Science, 4(2), 416–423. https://doi.org/10.1021/acsptsci.1c00034.
Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48(2), 175–187. https://doi.org/10.1016/j.neuron.2005.09.025.
Puxty, D. J., Ramaekers, J. G., de la Torre, R., Farré, M., Pizarro, N., Pujadas, M., & Kuypers, K. P. C. (2017). MDMA-induced dissociative state not mediated by the 5-HT2A receptor. Frontiers in Pharmacology , 8 Retrieved from https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00455.
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences, 98(2), 676–682. https://doi.org/10.1073/pnas.98.2.676.
Richards, W. A., & Barnard, G. W. (2016). Sacred knowledge; psychedelics and religious experiences. Columbia University Press.
Roozendaal, B., McEwen, B. S., & Chattarji, S. (2009). Stress, memory and the amygdala. Nature Reviews Neuroscience, 10(6), 423–433. https://doi.org/10.1038/nrn2651.
Roozendaal, B., & McGaugh, J. L. (2011). Memory modulation. Behavioral Neuroscience, 125(6), 797–824. https://doi.org/10.1037/a0026187.
Roseman, L., Leech, R., Feilding, A., Nutt, D. J., & Carhart-Harris, R. (2014). The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers. Frontiers in Human Neuroscience, 8. Retrieved from https://www.frontiersin.org/articles/10.3389/fnhum.2014.00204.
Sampedro, F., de la Fuente Revenga, M., Valle, M., Roberto, N., Domínguez-Clavé, E., Elices, M., … Riba, J. (2017). Assessing the psychedelic “after-glow” in ayahuasca users: Post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. The International Journal of Neuropsychopharmacology, 20(9), 698–711. https://doi.org/10.1093/ijnp/pyx036.
Sessa, B., Higbed, L., & Nutt, D. (2019). A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. Frontiers in Psychiatry, 10, 138. https://doi.org/10.3389/fpsyt.2019.00138.
Shapiro, S. L., Carlson, L. E., Astin, J. A., & Freedman, B. (2006). Mechanisms of mindfulness. Journal of Clinical Psychology, 62(3), 373–386. https://doi.org/10.1002/jclp.20237.
Shonin, E., Van Gordon, W., Compare, A., Zangeneh, M., & Griffiths, M. D. (2015). Buddhist-derived loving-kindness and compassion meditation for the treatment of psychopathology: A systematic review. Mindfulness, 6(5), 1161–1180. https://doi.org/10.1007/s12671-014-0368-1.
Simonds, C. H. (2023). View, meditation, action: A Tibetan framework to inform psychedelic-assisted therapy. Journal of Psychedelic Studies, 7(1), 58–68. https://doi.org/10.1556/2054.2023.00255.
Singleton, S. P., Wang, J. B., Mithoefer, M., Hanlon, C., George, M. S., Mithoefer, A., … Kuceyeski, A. (2023). Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder. Frontiers in Psychiatry, 13, 947622. https://doi.org/10.3389/fpsyt.2022.947622.
Smigielski, L., Kometer, M., Scheidegger, M., Krähenmann, R., Huber, T., & Vollenweider, F. X. (2019). Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat. Scientific Reports, 9(1), 14914–14923. https://doi.org/10.1038/s41598-019-50612-3.
Soler, J., Elices, M., Franquesa, A., Barker, S., Friedlander, P., Feilding, A., … Riba, J. (2016). Exploring the therapeutic potential of ayahuasca: Acute intake increases mindfulness-related capacities. Psychopharmacology, 233. https://doi.org/10.1007/s00213-015-4162-0.
Sottile, R. J., & Vida, T. (2022). A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy. Frontiers in Psychiatry, 13, 991753. https://doi.org/10.3389/fpsyt.2022.991753.
Sunjeev, K. K., Emma, J. K., Minchin, S., Moss, A., Lawn, W., Ravi, K. D., … Tom, P. F. (2015). Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’ and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices. Journal of Psychopharmacology, 29(9), 961–970. https://doi.org/10.1177/0269881115587143.
Taylor, R. L., Maurer, J. I., & Tinklenberg, J. R. (1970). Management of “bad trips” in an evolving drug scene. JAMA, 213(3), 422–425. https://doi.org/10.1001/jama.1970.03170290018003.
Uthaug, M. V., Lancelotta, R., van Oorsouw, K., Kuypers, K. P. C., Mason, N., Rak, J., … Ramaekers, J. G. (2019). A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology, 236(9), 2653–2666. https://doi.org/10.1007/s00213-019-05236-w.
Vargas, V., Dunlap, D., Dong, D., Carter, C., Tombari, T., Jami, J., … Olson, O. (2023). Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Science, 379(6633), 700–706. https://doi.org/10.1126/science.adf0435.
Zsadanyi, S. E., Kurth, F., & Luders, E. (2021). The effects of mindfulness and meditation on the cingulate cortex in the healthy human brain: A review. Mindfulness, 12(10), 2371–2387. https://doi.org/10.1007/s12671-021-01712-7.
