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Psilocybin improves performance in the set-shifting task. a Average trials-to-criterion across all sets in the baseline period (PRE, open gray circles) and in the acute psilocybin condition (PSI, blue circles, n = 15). ***p = 0.0005, paired t-test. b Number of completed sets in baseline and psilocybin conditions, p = 0.546, Wilcoxon sign-rank test. c Response time in baseline and psilocybin conditions. **p = 0.008, Wilcoxon sign-rank test. d Fraction of correct responses across all sets in baseline and psilocybin conditions. e Number of streaks of consecutive correct responses averaged across all sets, in baseline and psilocybin conditions. *p = 0.025, Wilcoxon sign-rank test. f Average length of streaks averaged across all sets, in baseline and psilocybin conditions. *p = 0.034, paired ttest. g Average trials-to-criterion for baseline (PRE, gray open circles) and saline conditions (SAL, brown circles, n = 14). h Number of completed sets in baseline and saline conditions. i Fraction of correct responses across all sets in baseline and saline conditions.
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Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A p...
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... psilocybin improves performance in set-shifting task Psilocybin (1 mg/kg, i.p.) improved performance on the setshifting task, as indicated by a significant decrease in the average number of trials rats needed to reach criterion ( (Fig. 2d, p = 0.188) but correct responses can be made without reaching the criterion of 10 consecutive ones. We, therefore, analyzed the effect of psilocybin on a "streak", defined as any series of consecutive correct responses. We observed that animals receiving psilocybin performed longer without making an incorrect response, resulting in ...
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... responses can be made without reaching the criterion of 10 consecutive ones. We, therefore, analyzed the effect of psilocybin on a "streak", defined as any series of consecutive correct responses. We observed that animals receiving psilocybin performed longer without making an incorrect response, resulting in fewer and longer streaks on average ( Fig. 2e, f; number of streaks, p = 0.025; average streak length, p = 0.041). These analyses suggest that psilocybin selectively reduces incorrect responses occurring after a series of correct ones, thus increasing the likelihood of reaching criterion on the ...
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... performed a number of additional analyses to investigate the effects of psilocybin in detail. First, we note that the effect of psilocybin on trials to criterion was most pronounced in the first two sets ( Supplementary Fig. S2a), possibly due to it wearing off in sets 3 and 4. To confirm that animals completed the first two sets while on the acute effects of psilocybin, we computed the time to criterion for each set during baseline and psilocybin days. Time to criterion values were similar in baseline and psilocybin days. ...
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... to criterion values were similar in baseline and psilocybin days. Furthermore, nearly all animals completed the first two sets within 30 min of starting the task, i.e., within 50 min of the injection ( Supplementary Fig. S2e), which is well within the time window for psilocybin's acute effects. Secondly, we analyzed Light-and Siderule sets separately to ask whether psilocybin differentially affected performance depending on rule, rather than order of sets. ...
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... we analyzed Light-and Siderule sets separately to ask whether psilocybin differentially affected performance depending on rule, rather than order of sets. These comparisons did not reach significance when looking at all four sets (data not shown; Light, p = 0.059; Side, p = 0.051), but they were both significant when we restricted the analysis to the first two sets (Supplementary Fig. S2f; Light, p = 0.026; Side, p = 0.024). We conclude that psilocybin had a similar effect on both Light and Side sets. ...
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... found no evidence of differences between baseline and psilocybin conditions (Supplementary Table S1). Finally, we note that data for both sexes were combined as no sex differences were found ( Supplementary Fig. S2g). ...
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... ensure that our stability criteria (see Supplementary Methods) resulted in stable baseline performance, we plotted trials to criterion, completed sets and fraction of correct responses on baseline, and on treatment days, for all psilocybin-treated animals. The behavior of individual animals oscillated within a consistent range across the baseline sessions, and the average across the cohort was stable ( Supplementary Fig. S2b). We also aimed to control for rule preference. ...
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... each animal we split sessions by whether their starting rule (i.e., in the first set) was a light or side rule, and quantified behavioral metrics for stable sessions performed by that animal. This analysis showed that for the psilocybin-treated cohort, performance as a group was not biased by the starting rule in each session ( Supplementary Fig. S2b). ...
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... receiving vehicle saline injections completed a similar number of sets as they did during the baseline period (Fig. 2h, p = 0.237, n = 14; see also Supplementary Fig. S2c, d), but they did not show any difference in the trials-to-criterion metric on the day of injection (Fig. 2g, p = 0.703). They also showed no change in the fraction of correct responses (Fig. 2i, p = 0.463). We used the saline-treated group as a control and compared trials to ...
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... receiving vehicle saline injections completed a similar number of sets as they did during the baseline period (Fig. 2h, p = 0.237, n = 14; see also Supplementary Fig. S2c, d), but they did not show any difference in the trials-to-criterion metric on the day of injection (Fig. 2g, p = 0.703). They also showed no change in the fraction of correct responses (Fig. 2i, p = 0.463). ...
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... receiving vehicle saline injections completed a similar number of sets as they did during the baseline period (Fig. 2h, p = 0.237, n = 14; see also Supplementary Fig. S2c, d), but they did not show any difference in the trials-to-criterion metric on the day of injection (Fig. 2g, p = 0.703). They also showed no change in the fraction of correct responses (Fig. 2i, p = 0.463). We used the saline-treated group as a control and compared trials to criterion during baseline for all treatment groups to the baseline value for the saline group. We found no difference, indicating that all treatment groups had similar ...
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... vehicle saline injections completed a similar number of sets as they did during the baseline period (Fig. 2h, p = 0.237, n = 14; see also Supplementary Fig. S2c, d), but they did not show any difference in the trials-to-criterion metric on the day of injection (Fig. 2g, p = 0.703). They also showed no change in the fraction of correct responses (Fig. 2i, p = 0.463). We used the saline-treated group as a control and compared trials to criterion during baseline for all treatment groups to the baseline value for the saline group. We found no difference, indicating that all treatment groups had similar pre-treatment performance in the task (Supplementary Fig. S2h; two-way ANOVA followed by Dunnett's ...
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... used the saline-treated group as a control and compared trials to criterion during baseline for all treatment groups to the baseline value for the saline group. We found no difference, indicating that all treatment groups had similar pre-treatment performance in the task (Supplementary Fig. S2h; two-way ANOVA followed by Dunnett's test, all p > 0.35). We also compared each group's treatment data with that of the saline group and found a significant difference for psilocybin (Supplementary Fig. S2h; twoway ANOVA followed by Dunnett's test, p = 0.005), among others (see below). ...
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... found no difference, indicating that all treatment groups had similar pre-treatment performance in the task (Supplementary Fig. S2h; two-way ANOVA followed by Dunnett's test, all p > 0.35). We also compared each group's treatment data with that of the saline group and found a significant difference for psilocybin (Supplementary Fig. S2h; twoway ANOVA followed by Dunnett's test, p = 0.005), among others (see below). ...
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... Fig. S3). Moreover, rats completed significantly fewer sets when treated with DOI compared to the baseline period (Fig. 4b, p = 0.012), with most completing only one or no sets at all. The fraction of correct responses was also lower compared to baseline (Fig. 4c, p = 0.005). In the comparison to saline, the DOI group showed a significant effect (Fig. S2h, p = 0.013). However, we argue that the low value for trials to criterion in the DOI group is largely due to artificially low numbers for that metric when animals complete very few sets, as explained above. Most animals treated with DOI only completed one set or none at all. Overall this represents a clear deficit in performance of ...
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... of either psilocybin or saline. Ketanserin blocked the effect of psilocybin on cognitive flexibility (Fig. 5a−c, n = 14; trials to criterion, p = 0.231; completed sets, p = 0.688; fraction correct, p = 0.469; see also Supplementary Fig. S4). This was also evident when comparing the ketanserin + psilocybin group to the saline control group (Fig. S2h, p = 0.431). We therefore conclude that the effects of psilocybin are at least partly mediated by its action at 5HT2A ...
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... animals. They required fewer trials to reach criterion (Fig. 5d, p = 0.026, n = 11), while completing a similar number of sets as during baseline (Fig. 5e, p = 0.680), and showed a subtle but significant increase in the percent of correct trials (Fig. 5f, p = 0.050). We also found a significant effect when comparing to the saline control group (Fig. S2h, p = 0.0004). This effect of ketanserin is consistent with a previous report [35] and suggests a complex relationship between 5HT2A receptor function and cognitive ...
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The title compound, C12H16N2O, is a hydroxy-substituted monoamine alkaloid, and the primary metabolite of the naturally occurring psychedelic compound psilocybin. Crystalline forms of psilocin are known, but their characterization by single-crystal structure analysis is limited. Herein, two anhydrous polymorphic forms (I and II) of psilocin are d...
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... This study contrasts with previous preclinical psychedelic reversal learning studies in terms of drug administration timepoints (46)(47)(48)(49)(50). We administered the psychedelic or saline control 15 days before the start of the reversal protocol. ...
... In a two-choice visual discrimination task, 25CN-NBOH (1-2 mg/kg) was found to have no significant effects on reversal learning in mice when administered acutely, immediately before testing (49). Other previous rodent studies using attentional set-shifting and T-maze paradigms found impairment of flexible learning with acute administration of the psychedelics DOI (1 mg/kg) or 25CN-NBOH (1 mg/kg) on cognitive flexibility (48,50). However, one study found the enhanced cognitive flexibility with acute psilocybin (1 mg/kg) in the same attentional set shifting paradigm that found impairment following administration of DOI (50). ...
... Other previous rodent studies using attentional set-shifting and T-maze paradigms found impairment of flexible learning with acute administration of the psychedelics DOI (1 mg/kg) or 25CN-NBOH (1 mg/kg) on cognitive flexibility (48,50). However, one study found the enhanced cognitive flexibility with acute psilocybin (1 mg/kg) in the same attentional set shifting paradigm that found impairment following administration of DOI (50). The differences in the acute effects of psychedelics on reversal learning may be due to the study design, discussed below, as well as a combination of drug and dose. ...
Psychedelic drugs have shown therapeutic potential for the treatment of multiple neuropsychiatric disorders chiefly by promoting long-lasting plasticity in the prefrontal cortex (PFC). A critical function of the PFC is the ability to apply previously learned rules to novel scenarios, a skill known as cognitive flexibility. Here, we show that a single dose of 25CN-NBOH, a serotonin 2A receptor-preferring psychedelic, improves performance on a relatively complex flexible reversal learning task in mice, measured 2-3 weeks after the dose. This effect was seen in both male and female mice. This behavioral finding complements previous cellular results showing that a single psychedelic dose induces long-term structural changes in the PFC and uniquely demonstrates sustained improvements in cognitive flexibility in a novel behavioral paradigm weeks after the initial psychedelic dose in mice. This high throughput task also provides a rapid, automated way to assess other candidate psychedelics for their impact on cognitive flexibility in mice.
... Previous studies on psilocybin and decision-making indicate that psilocybin may improve cognitive flexibility [72][73][74]; a further study found that psilocybin may reduce punishment by changing one's concerns for the outcome of their game partner in a social decision-making task [73]. The current findings add to a growing literature in this area highlighting a range of effects that emerge in different task contexts, and which perhaps have similar underlying mechanisms. ...
Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit active inference and reinforcement learning computational models to a novel two-armed bandit reversal learning task capable of capturing engagement behaviour in rats. The model revealed that after receiving psilocybin, rats achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.
... Psilocybin will be kept at -20ºC for storage throughout the experiment [16]. The compound will be dissolved in a saline solution and diluted to a concentration of 1mg/ml. . ...
Introduction: Huntington’s Disease (HD) is a progressive, neurodegenerative disease that causes significant amounts of neuron death in the brain. It is a genetic disorder, resulting from the over-repetition of the CAG sequence in the gene that codes for the huntingtin protein. Currently, there are no viable cures or treatments to slow or stop the progression of this disorder, making it a target candidate for treatment research. However, given the difficulty and complexity of in treating the genetic cause of HD in adults, a more viable approach may involve treating the resulting neurodegeneration with neuroprotective compounds, such as psilocybin. As such, our study proposes the usage of psilocybin to treat HD due to its neuroprotective, neurotrophic, and neuroplastic effects, resulting in a decreased rate of neuron loss and increased synaptic density. Methods: We propose an in-vivo experiment using several groups of zQ175 knock-in (KI) mice, which will mimic HD in the mice. Following 8 weeks, the mice’s brains will be extracted at different time intervals to analyze the progression of neuronal death using histology and immunohistochemistry, which should inform us about the progression of HD in the different groups of mice. Moreover, throughout this experiment, the motor control of the mice will be observed using the rotarod test, the raised beam test, and the footprint test. Data from these tests will act as behavioral markers for HD, providing an alternate source of information on the progression of HD in the mice. Expected Results: KI mice are expected to have lower rates of neuronal death, higher amounts of synaptic density, and higher scores on average across the three motor behavior tests, compared to the non-treated KI mice. Discussion: These results could provide insight into potential treatments for slowing the progression of HD. If successful, possible next steps could be to determine the efficacy of psilocybin in clinical trials for HD. Conclusion: This study is expected to provide information on the usage of psilocybin as a treatment for HD. If the expected results are obtained, psilocybin may help improve the quality of life for those afflicted with HD.
... In rodents, acute administration of psilocybin has been observed to enhance cognitive flexibility, with specificity noted in the augmentation of switching between previously learned behavioral strategies rather than influencing Pavlovian reversal learning. The 5HT 2AR antagonist ketanserin was found to attenuate psilocybininduced effects on set-shifting, while a 5HT2C-selective antagonist exhibited no such influence (Torrado Pacheco et al., 2023). For healthy adults and individuals with Major Depressive Disorder (MDD), psilocybin treatment has shown promise in augmenting cognitive and neural flexibility (Doss et al., 2021;Nayak et al., 2023). ...
Alzheimer’s disease (AD) stands as a formidable neurodegenerative ailment and a prominent contributor to dementia. The scarcity of available therapies for AD accentuates the exigency for innovative treatment modalities. Psilocybin, a psychoactive alkaloid intrinsic to hallucinogenic mushrooms, has garnered attention within the neuropsychiatric realm due to its established safety and efficacy in treating depression. Nonetheless, its potential as a therapeutic avenue for AD remains largely uncharted. This comprehensive review endeavors to encapsulate the pharmacological effects of psilocybin while elucidating the existing evidence concerning its potential mechanisms contributing to a positive impact on AD. Specifically, the active metabolite of psilocybin, psilocin, elicits its effects through the modulation of the 5-hydroxytryptamine 2A receptor (5-HT2A receptor). This modulation causes heightened neural plasticity, diminished inflammation, and improvements in cognitive functions such as creativity, cognitive flexibility, and emotional facial recognition. Noteworthy is psilocybin’s promising role in mitigating anxiety and depression symptoms in AD patients. Acknowledging the attendant adverse reactions, we proffer strategies aimed at tempering or mitigating its hallucinogenic effects. Moreover, we broach the ethical and legal dimensions inherent in psilocybin’s exploration for AD treatment. By traversing these avenues, We propose therapeutic potential of psilocybin in the nuanced management of Alzheimer’s disease.
... findings support the notion that psychedelics specifically reduce sustained attention or vigilance but not cognitive control (as is needed for accuracy-based tasks). Additional confirmatory evidence is provided by research regarding creative performance under the influence of psychedelics 99,111,186 and animal research 187,188 showing an increased ability to switch action patterns under psilocybin. Furthermore, this model of increased cognitive flexibility aligns with results regarding neuropsychological consequences of long-term psychedelic use. ...
Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute (“afterglow”) window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.
... Nevertheless, it is intriguing to hypothesize that rapid neuroplasticity induced by ketamine or psilocybin produces therapeutic effects by virtue of modifying how affective or cognitive events are processed. One possibility is that increased plasticity is related to enhancements in cognitive flexibility that have been observed in humans and rodents upon psilocybin administration (76,77). Alternatively, it could be a question of reopening a critical period of plasticity relevant to traumatic memories, emotional processing, or development of the self (78). ...
... Previous studies on psilocybin and decision-making indicate that psilocybin may improve cognitive flexibility (69)(70)(71); a further study found that psilocybin may reduce punishment by changing one's concerns for the outcome of their game partner in a social decision-making task (70). The current findings add to a growing literature in this area highlighting a range of effects that emerge in different task contexts, and which perhaps have similar underlying mechanisms. ...
Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit computational models of underlying decision-making mechanisms to behaviour in rats. The model revealed that rats treated with psilocybin achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.
... The chosen dosage of DOI has been shown to elicit a robust head twitch response, a behavioral marker for hallucinogenic effects, 65,66 and consistent behavioral effects. 67,68 For ketamine, 10 mg/kg is commonly used in preclinical models of psychiatric disorders and has demonstrated robust and long-lasting neural and behavioral changes at this dose. ...
Introduction: Serotonergic psychedelics and ketamine produce rapid and long-lasting symptomatic relief in multiple psychiatric disorders. Evidence suggests that despite having distinct molecular targets, both drugs may exert therapeutic benefit via their pro-neuroplastic effects. Following treatment with ketamine or serotonergic psychedelics, patients are reported to be more open to behavioral change, which is leveraged for psychotherapy-assisted reframing of narratives of the self. This period of enhanced behavioral change is postulated to be supported by a post-treatment window of enhanced neural plasticity, but evidence for such “metaplastic” effects is limited. In this study, we tested for neural plasticity and metaplasticity in murine hippocampus.
Methods: Brain slices were obtained from C57BL/6J mice 24 h after treatment (intraperitoneal injection) with saline, ketamine, or the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Extracellular fiber volleys (FVs) and field excitatory postsynaptic potentials (fEPSPs) were recorded in stratum radiatum of CA1 in response to stimulation of Schaffer collateral fibers before and after induction of short-term potentiation (STP) and long-term potentiation (LTP).
Results: Before LTP induction, responses differed across treatment groups (F2,67 = 5.407, p = 0.00665), with fEPSPs enhanced in slices from DOI-treated animals (p = 0.0182), but not in ketamine-treated animals (p = 0.9786), compared with saline. There were no treatment effects on LTP (F2,56 = 0.6, p = 0.516), but there were on STP (F2,56 = 4.409, p = 0.0167), with enhanced STP in DOI-treated animals (p = 0.0352), but not in ketamine-treated (p = 0.9999) animals, compared with saline. A presynaptic component to the mechanism for the DOI effects was suggested by (1) significantly enhanced FV amplitudes (F2,61 = 3.17, p = 0.049) in DOI-treated animals (p = 0.0457), but not in ketamine-treated animals, compared with saline (p = 0.8677); and (2) enhanced paired pulse ratios (F2,61 = 3.581, p = 0.0339) in slices from DOI-treated animals (p = 0.0257), but not in ketamine-treated animals (p = 0.4845), compared with saline.
Conclusions: DOI, but not ketamine, induced significant neuroplastic and metaplastic effects at hippocampal CA1 synapses 24 h after treatment, likely in part via a presynaptic mechanism.
... Given the growing appreciation in behavioural neuroscience that these types of behavioural tests (i.e. the forced swim test) do not reliably translate to human depressive syndromes [35] and that reinforcement learning tasks offer key advantages including more relevant clinical links and repeatability [36], these early approaches clearly need to be redressed. Other key methodological details in prior studies need to be considered, particularly the role of multiple dosing (cross-over) designs, antagonising 5-HT2AR with ketanserin (a compound with many known non-serotonergic binding sites [37]), and the measurable motoric side effects of acute psilocybin administration [38]. ...
... Not only does ketanserin bind multiple serotoninergic and non-serotonergic receptors but it also only blocks~30% of 5-HT2AR in the rat cortex [76]. It is plausible, therefore, that partial blockade with ketanserin shifts the binding of psilocybin to other 5-HTR subtypes, including 5-HT1A, which may explain the acute improvement in reversal learning after ketanserin alone previously reported in rats [38]. ...
... If adaptive cognition requires an appropriate balance between 5-HT1A and 5-HT2A receptor function [49], our molecular findings suggest that individuals exhibiting elevated 5-HT1AR function (or for that matter reduced 5-HT2AR function) may not respond positively (since further elevation or reduction elicited by psilocybin would push them into the tail ends of the inverted "U"). It is also important to note, in light of the recent observation that psilocybin, administered acutely, did not facilitate flexibility [38], that there are important methodological differences that may explain this discordance. Specifically, we examined effects of psilocybin post-acutely, using a single administration paradigm, and the reversal learning task used in the present study relied on action-outcome learning rather than Pavlovian cue-outcome learning. ...
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.
... Psychedelic treatments may enhance the brain mechanisms underlying psychotherapeutic change, perhaps by opening a window of enhanced neural plasticity (Lepow et al., 2023). Psychedelic treatment may augment nonspecific but potent mechanisms of change associated with psychotherapy more generally (Gukasyan & Nayak, 2021) or may enhance more specific psychotherapeutic processes, such as the development of value-based living (Sloshower et al., 2020), extinction learning (Feduccia & Mithoefer, 2018), or cognitive flexibility (Torrado et al., 2023). ...
Novel treatments are required for the 30-50% of individuals with obsessive-compulsive disorder (OCD) who remain resistant to first-line pharmacological and psychotherapeutic treatments. Recent pilot data suggest benefit from psilocybin-assisted psychotherapy (PAP) and from imagery rescripting (ImRs). We explore psychological mechanisms of change underpinning both interventions that appear to allow for reprocessing of negative emotions and core beliefs associated with past aversive events. A next critical step in PAP is the development of psychotherapeutic frameworks grounded in theory. We propose that basing PAP on an ImRs framework may provide synergistic benefits in symptom reduction, modification of core beliefs, and value-based living.
