Psychedelic Research Papers

In this open label study (n=24) depressed patients were given psilocybin (25mg/70kg) and the effects of psilocybin therapy on cognitive flexibility, neural flexibility and neurometabolite concentrations were assessed. While it was found that depressive symptoms were reduced, interestingly, it was also found that increased dynamics of functional connectivity (dFC) between the anterior and posterior cingulate cortices (ACC/PCC) predicted improvements in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility.

This paper (2022) reviews the current state of research regarding the effect psychedelics have on different aspects of cognition. The gaps regarding the acute effects psychedelics have on cognition are discussed as well as the findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.

This study (n=86) assessed the effects of six infusions of ketamine (35mg/70kg) over 2 weeks on suicidality in patients with depression. Next to the Beck Scale for Suicide Ideation (SSI) and the Montgomery-Asberg Depression Rating Scale (MADRS), the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery was also used. MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation.

This study (n=48) investigates the ‘afterglow’ effects of ayahuasca, focusing on improved mindfulness and cognitive flexibility to study its psychological mechanisms using Five Facets Mindfulness Questionnaire (FFMQ), Experiences Questionnaire (EQ), Cognitive Flexibility Scale (CFS), Wisconsin Picture Card Sorting Task (WPCST) and Stroop tests. The study findings reported that further changes in cognitive flexibility in the ‘afterglow’ period do occur and also supports the therapeutic potential of ayahuasca to improve mindfulness for naïve and experienced ayahuasca users.

This pre-print (n=106) investigated the association between hallucinogen use, macroscale brain structure, personality, cognitive ability, and illicit drug use in a naturalistic sample. Hallucinogen users scored higher on measures of openness to new experiences, and cognitive ability, and had a greater density of structural connectivity in white matter tracts that are thought to support cognition, emotion, and creativity.

This open-label study (n=58) compared the effects of a single dose of ketamine (35-56.7mg/70kg) on the cognitive effects of those suffering from depression (MDD; n=14) or PTSD (n=15) and healthy control subjects (n=29). The study found acute declines in attention, executive function, and verbal memory. Only the effect on attention was larger in the patient groups. The baseline cognitive function of participants didn't predict clinical outcomes.

This review (s=42 studies) offers an overview of the effects of psilocybin on cognition and creativity. It was found that shortly after the intake of psilocybin, cognition and creativity are impaired, especially with higher doses, but these effects diminish over time and some positive effects may emerge.

In this study, subjects with unipolar (n=84) and bipolar (n=27) depression experiencing treatment resistance or suicidality received six infusions of ketamine (35mg/70kg) over a 12-day period. It was found that ketamine has a pro-cognitive effect on processing speed and that this effect may be independent of ketamine's effect on mood. The clinical outcomes related to ketamine may be partly mediated by improvements in cognition.

This literature review (2019) discusses controlled experimental studies on the effects of psychedelics (e.g. LSD, psilocybin, MDMA) on social cognition and behavior to treat disorders characterized by social dysfunctions such as depression, post-traumatic stress disorder (PTSD), anxiety, and autism spectrum disorders (ASD). It also discusses persisting knowledge gaps into sex-specific drug effects and objective data on social behavior within the framework of MDMA- and hallucinogen-assisted therapy. The study suggests hallucinogen-based treatment methods and the development of novel medication for trans-diagnostic dysfunction in social cognition and noted that entactogens and hallucinogens have consistently shown prosocial effects and have identified alterations in social processing and behavior as major factors for the efficacy of treatments involving them.

This double-blind placebo-controlled preprint study (n=34) assessed the effects of microdosing psilocybin (0.5g dried mushrooms, about 0.9mg psilocybin) on subjective experience, behaviour, creativity, perception, cognition, and brain activity. Participants received two doses (psilocybin/placebo) administered separately, one week apart. Subjective effects were more intense for the active dose, while null effects or a trend towards cognitive impairment were observed. Expectation effects may be, in part, responsible for the anecdotal benefits of microdosing.

This double-blind placebo-controlled cross-over study (n=20) found that psilocybin (18.2mg/70kg) disrupted certain auditory-related brain signals (P300, not MMN) which decreased in amplitude in correlation with higher psilocin serum levels (and more intense psychedelic experiences).

This trial (n=24) investigated the effects LSD (50 μg) has on cognition in healthy volunteers. It was found that LSD sub-acutely improved visuospatial memory and phonological verbal fluency and impaired cognitive flexibility when compared to placebo.

This correlational study (n=176) investigated the long-term residual psychological and cognitive effects of peyote use amongst native American Church members, compared between regular users (n=61), minimal users (n=79), and members with a history of alcohol dependence (n=36). Only members with prior alcohol dependence showed neuropsychological deficits, but there was no link between psychological or cognitive deficits linked to peyote use.

This randomized-controlled trial (n=51) assessed the short-term effects of three subanesthetic esketamine infusions (17.5mg/70kg) in adolescents aged 13–18 with major depressive disorder (MDD) and suicidal ideation. The study found a significant improvement in processing speed and working memory in the esketamine group from baseline to days 6 and 12, with no harm to cognition observed. However, there was no significant association between baseline cognition and the antidepressant or antisuicidal effects of esketamine.

This meta-analysis (n=1,298) explored the effects ketamine has on cognition, anxiety, quality of life, and social functioning in adults with psychiatric disorders. Ketamine was found to have positive effects on depression, anxiety and social functioning but not with respect to cognition and quality of life.

This meta-analysis assessed the effects of ketamine administration in healthy participants (n=1,041) on several cognitive domains. Deficits in verbal learning/memory were most prominent, whereas response inhibition was the least affected. Negative effects were dependent on infusion dose and plasma level but unaffected by enantiomer type, route of administration, sex or age.

This observational within-subjects study (n=17) repeatedly assessed participants during their psychedelic microdosing regimen using the CNSVS neurocognitive battery in a naturalistic setting. Results indicate that neither the day of microdosing nor the day after showed significant links to enhanced or diminished performance across various cognitive functions. The study concludes that microdosing psychedelics might influence psychological pathways rather than neurocognitive ones, leading to a subjective feeling of performance enhancement.

This double-blind, placebo-controlled study (n=20) with psilocybin (10, 20, 30mg/70kg) and DMX (400mg/70kg) finds no global cognitive impairment. The study does find (for both drugs) effects on psychomotor performance, working memory, episodic memory, associative learning, and visual perception.

In this study in mice, a deficiency in mGluR2 function (receptor for the neurotransmitter glutamate) was identified as a common mechanism for increased alcohol-seeking behaviour and impaired cognitive flexibility in rodent models of alcohol use disorder (AUD). Psilocybin was shown to restore prefrontal mGluR2 levels and reduce relapse behaviour. Researchers suggest a biomarker approach to target this neuronal mechanism, implying that psilocybin can treat AUD physiologically as well as psychologically, as other research has suggested.

This preprint review (2021) surveys the literature on cognition and neuroimaging studies that have investigated functional and structural changes associated with MDMA use. It concludes that the neurocognitive/neurophysiological changes that occur with repeated MDMA use are potentially reversible over time.

This study (n=18) used psilocybin administration in order to investigate the neuropharmacology of schizophrenia. The authors suggest that 5-HT2A and NMDA receptors may be involved in the cognitive deficits observed in schizophrenic individuals.

This legal commentary (2016) advocates for drug-policy reform on the grounds of a liberal rights-based approach that invokes the notion of cognitive liberty as a crucial component of freedom of thought, enshrined within Article 9 of the European Convention on Human Rights (ECHR). On this basis, it is proposed that drug policy should move beyond harm-reduction strategies and calling for exemptions from criminalization on therapeutic or religious grounds, and establish a right to control one’s own consciousness via psychoactive substances, and apply policies that maximize their benefits.

This case study (n=2) describes the treatment methodology of MDMA (112.5mg) -assisted Cognitive-Behavioral Conjoint Therapy administered to a PTSD patient in conjunction with his romantic partner. Through the therapeutic context, set, and setting that entailed multiple days of participant engagement and the empathy-inducing effects of the MDMA, the procedure created strong therapeutic bonds between the couple and the therapists and facilitated the resolution of PTSD symptoms and improvement in relationship satisfaction.

In this randomized, double-blind study (n=5) the MDMA like drug (S)-MDE and (R)-MDE were tested for their effect on mood, cognition and brain activity.

This rat model of Fragile X syndrome (FXS, genetic cause of autism - ASD) finds that microdoses of psilocybin normalise cognitive performance in an object recognition test.

This paper (2022) explores historical and sociological influences on current psychedelic administration in mainstream European and American clinical research settings. It considers these dynamics in relation to cognitive-behavioural therapies (CBT) and acceptance and commitment therapy (ACT). The paper advocates for CBTs for several reasons, such as the large base of empirical evidence they have. Several types of CBTs are discussed and how they can be used to inform the preparation, session, and integration phases of psychedelic psychotherapy.

This survey study (n=803) assessed the credibility rating of cognitive-behavioural therapy (CBT) and psilocybin-assisted therapy (PAT) among individuals reporting depressive symptoms. CBT was rated as more credible than PAT, while men and lifetime psychedelic users rated PAT more credible than women and non-users with few other predictors accounting for variance in credibility.

This systematic review & meta-analysis (2024; s=10; n=304) synthesized data from contemporary studies, including both randomized and non-randomized controlled trials, to evaluate lasting effects of serotonergic psychedelics on cognition, creativity, emotional processing, and personality. Overall, no statistically significant effects were observed for most outcome measures; however, a meta-analysis of emotional recognition outcomes revealed faster reaction times in the active treatment groups for disgust and sadness.

This open-label study (n=12, 6 couples) describes the safety, tolerability, and efficacy of MDMA in combination with cognitive-behavioral conjoint therapy (CBCT) where one half of the couple was battling with PTSD.

This open-label study (n=25) explored the effects of using intravenous ketamine to treat treatment-resistant depression (TRD) in participants over the age of 60. Depressive symptoms improved significantly, 48% of participants responded, and during the acute phase, executive function measures and the fluid cognition composite score improved (Cohen's d = 0.61).