TABLE 1.
Recent (2008–2021) clinical trials assessing social behaviour-related effects of psychedelics in neurotypical (non-ASD) individuals
| Year | Title | Cohort | Design | Compound | Regimen (dose, frequency, route of administration) | Main outcomes | Side effects | Ref |
|---|---|---|---|---|---|---|---|---|
| 2008 | Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later | Healthy volunteers with regular participation in religious/spiritual activities | Randomized, double-blind, placebo-controlled, within-subject | Psilocybin | 30 mg/70 kg once, twice or three times | Psilocybin increases altruistic/positive social effects at 14 months follow-up | None reported | Griffiths et al. (2008) |
| 2009 | A six-month prospective evaluation of personality traits, psychiatric symptoms and quality of life in ayahuasca-naïve subjects | Volunteers participating in religious Ayahuasca rituals (18–57 y/o, average 35.7 y/o, n = 23, 8 males, 15 females) | Observational naturalistic study | Ayahuasca | Up to 12 times over 6 months | Regular ayahuasca users have higher “social functioning” scores in the Short Form-36 Health Survey Questionnaire Ayahuasca might lower social reward dependence by decreasing sensitivity to signals of social approval |
None reported | Barbosa et al. (2009) |
| 2011 | Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects | Healthy volunteers (29–62 y/o average 46 y/o, n = 18, 8 males, 10 females) | Randomized, double-blind, placebo-controlled, within-subject | Psilocybin | 0, 5, 10, 20, 30 mg/70 kg, per oral solution | Psilocybin increases altruistic/positive social effects at all doses tested | Psilocybin induces dose-dependent acute anxiety/fear 44% of volunteers report delusions or paranoid thinking sometime during the session (especially at 30 mg/70 kg). Effects managed with reassurance in the supportive setting | Griffiths et al. (2011) |
| The increase in altruistic/positive social effects elicited by psilocybin 20–30 mg/70 kg are greater than those elicited by psilocybin (0.5–10 mg/70 kg) | ||||||||
| The increase elicited by psilocybin (20–30 mg/70 kg) in altruistic/positive social effects remains present at 14 months follow-up | ||||||||
| Volunteers reported better social relationships with family and others | ||||||||
| 2015 | Acute effects of lysergic acid diethylamide in healthy subjects | Healthy volunteer (25–51 y/o, average 28.6 y/o, n = 16, 8 males, 8 females) | Randomized, double-blind, placebo-controlled, within-subject | LSD | 200 μg, once, gelatin capsules | LSD increases ratings of “empathogenic drug effects” such as “closeness to others,” “openness,” and “trust” LSD increases circulating oxytocin level |
No severe acute side effects | Schmid et al. (2015) |
| Most frequent acute or sub-acute mild side effects (up to 72 h): difficulty concentrating, headache, exhaustion, dizziness, lack of appetite, dry mouth, imbalance, nausea | ||||||||
| 2016 | LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality | Healthy volunteer and mostly hallucinogen-naive (25–65 y/o) volunteers, n = 40, 20 males, 20 females) | Randomized, double-blind, placebo-controlled, within-subject | LSD | 100 μg, once, per oral solution | LSD enhances explicit and implicit emotional empathy LSD increases prosocial behaviour LSD enhances the desire to be with other people LSD decreases cognitive empathy |
None reported | Dolder et al. (2016) |
| 200 μg, once, per oral solution | ||||||||
| 2016 | Effects of serotonin 2A/1A receptor stimulation on social exclusion processing | Healthy volunteers (20–37 y/o, average 26.48, n = 21, 12 males, 9 females) | Randomized, double-blind, placebo-controlled, within-subject | Psilocybin | 0.215 mg/kg, once, per oral solution | Psilocybin reduces the feeling of social rejection Psilocybin decreases the neural responses to social exclusion in the dorsal anterior cingulate cortex and the middle frontal gyrus | None reported | Preller et al. (2016) |
| 2016 | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial | Individuals with advanced (stage III or IV) cancer (n = 29) | Randomized, double-blind, placebo-controlled, within-subject | Psilocybin | 0.3 mg/kg, per oral solution, once | Psilocybin immediately reduced anxiety and depression symptoms for up to 7 weeks post-treatment | None reported | Ross et al. (2016) |
| Psilocybin decreased cancer-related demoralization and hopelessness while increasing spiritual well-being and quality of life for up to 6.5 months post-treatment | ||||||||
| Psilocybin produced positive social effects (ex: increased altruism), positive mood changes and positive changes on attitudes about life and self | ||||||||
| 2016 | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial | Individuals with a life-threatening cancer diagnosis (average age: 56.3 y/o, n = 51, 26 males, 25 females) | Randomized, double-blind, crossover | Psilocybin | Low dose: 1 or 3 mg/70 kg High dose: 22 or 30 mg/70 kg Either low or high dose was administered, then after 5 weeks the other dosage was administered | High-dose psilocybin elicited a clinician- and self-rated decrease in anxiety (including death anxiety) and depressed mood, and an increase in quality of life and optimism Effects were still present in >80% of individuals at a 6-months follow-up evaluation |
No serious adverse effects | Griffiths et al. (2016) |
| Some minor adverse effects (such as psychological discomfort, elevated blood pressure, nausea) occurred during the psilocybin session | ||||||||
| 2017 | Effect of Psilocybin on Empathy and Moral Decision-Making | Healthy volunteers (20–38 y/o, average 26.72 y/o, n = 32, 17 males, 15 female) | Randomized, double-blind, placebo-controlled, within-subject | Psilocybin | Psilocybin 0.215 mg/kg, per oral solution | Psilocybin increases explicit and implicit emotional empathy compared with placebo Psilocybin does not modify cognitive empathy compared to placebo | None reported | Pokorny et al. (2017) |
| 2017 | Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviours | Healthy volunteers, support for spiritual practice (n = 75) | Randomized, double-blind, placebo-controlled | Psilocybin | Very low dose - Psilocybin 1 mg/70 kg (0.0143 mg/kg) per oral solution, twice 1 month apart n = 25 High dose - Psilocybin 20 and 30 mg/70 kg (0.29 mg/kg and 0.43 mg/kg) respectively in session 1 and 2, 1 month apart (+standard support for spiritual practice, n = 25, + high support for spiritual practice, n = 25) | Individuals receiving high dose psilocybin score higher for altruistic/positive social effects than those receiving low dose psilocybin | None reported | Griffiths et al. (2018) |
| Individuals receiving high dose psilocybin + high support for spiritual practice score higher for altruistic/positive social effects acutely than dose receiving high dose psilocybin + standard support | ||||||||
| At 6 months follow-up, individuals who received high dose psilocybin score higher for altruistic/positive social effects than those receiving low dose psilocybin on altruistic/positive social effects | ||||||||
| At 6 months follow-up, individuals receiving high dose psilocybin + high support for spiritual practice score higher than those receiving high dose + standard support on altruistic/positive social effects | ||||||||
| 2017 | Long-term follow-up of psilocybin-facilitated smoking cessation | Individuals with tobacco addiction (average 51 y/o, n = 15, 10 males, 5 females) | Open label pilot study (follow-up) | Psilocybin | 20 and 30 mg/70 kg, two-three times | Altruistic/positive social effects scores remain significantly higher compared to baseline at 12 months follow-up after the first administration | Physiological adverse effects limited to mild post-session headache, and modest acute elevations in blood pressure and heart rate Some participants experienced challenging (fearful, anxiety-provoking) psilocybin session experiences. These effects resolved by the end of the drug session via interpersonal support from study staff | Johnson et al. (2017) |
| 2018 | Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study | Healthy volunteers (20–34 y/o, mean age 25.42 y/o, n = 24, 18 males, 6 females) | Randomized, double-blind, placebo-controlled, within-subject | LSD | LSD 100 μg, once, per oral solution | LSD loosens self-boundaries, reducing neural response to self- versus other-initiated real-time social interaction LSD’s reduction in brain activity in regions implicated in self-processing and social cognition was correlated with subjective drug effects LSD alters joint attention processing in the mPFC |
No serious adverse events Transient mild headaches after drug effects wore off (n = 4 participants) Transient sleep disturbances for the first 2 nights after drug administration (n = 1 participant) |
Preller, Schilbach, et al. (2018) |
| Ketanserin | Ketanserin 40 mg/kg, per oral solution, once prior to LSD 100 μg | LSD increases positive and negative affect scores | No further side effects reported after 3 months | |||||
| Ketanserin blocked the LSD-induced changes in self-processing and social cognition | ||||||||
| 2018 | Long-lasting subjective effects of LSD in normal subjects | Healthy volunteers (n = 16) | Randomized, double-blind, placebo-controlled, within-subject (follow-up) | LSD | 200 μg, once, per oral solution | LSD increases ratings of altruistic/positive social effects after 1 and 12 months | None reported | Schmid and Liechti, (2018) |
| 2019 | Psilocybin and MDMA reduce costly punishment in the Ultimatum Game | Healthy volunteers (male, n = 20) | Open-label, within-participant design | Psilocybin | 2 mg per intravenous infusion over 2 min (test performed 60 min later) | Psilocybin increases one’s concern for the outcome of interacting partners | None reported | Gabay et al. (2018) |
| 2019 | Acute subjective and behavioural effects of microdoses of LSD in healthy human volunteers | Healthy volunteers (18–40 y/o, n = 20, 8 males, 12 females) | Randomized, double-blind, placebo-controlled, within-subject | LSD | LSD 6.5, 13, or 26 μg, per oral solution with tartaric acid (0.5 ml, sublingual) | Dose-related subjective drug effects LSD (26 µg) increased vigor and marginally decreased the positivity ratings for positive pictures |
Trend towards increased anxiety with 26 µg dose | Bershad et al. (2019) |
| No other effects on mood, cognition or physiological measures | ||||||||
| 2019 | Replication and extension of a model predicting response to psilocybin | 183 valid responses (n = 97 males, n = 85 females). Average age 31.9 y/o, range 18–70 years | Retrospective survey | Psilocybin (dried mushrooms in pieces, dried powdered mushrooms, fresh mushrooms, synthesized psilocybin) Other unprescribed (such as cannabis, opiates, alcohol, stimulants), and prescribed (antidepressant, anxiolytic, blood pressure medications) substances ingested by some of the respondents | Various amounts ingested in the previous 12 months | Having a complete mystical experience is associated with higher post-treatment scores of empathy and social concern Surrender and preoccupation are the psychological states that produce the greatest (respectively positive and negative) responses |
None reported | Russ et al. (2019) |
| 2019 | Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being | Volunteers attending a psilocybin retreat (average 34.8 y/o, n = 55, 24 males, 26 females) | Observational naturalistic study | Psilocybin-containing truffles | 34.2 g average of psilocybin-containing truffles in tea form, once. Psilocybin content 0.127 mg/G of truffle (content in 34.2 g = 4.34 mg psilocybin) Psilocin—0.7 mg/G of truffle (content in 34.2 g = 23.9 mg psilocin) Truffles crushed and boiling hot ginger tea added. Truffles remains in the cup eaten optionally |
Increased emotional empathy (concern for faces depicting negative emotions) sub-acutely (the morning after) but not after 7 days | None reported | Mason et al. (2019) |
| Increased implicit arousal in response to faces depicting positive and negative emotional content the morning after Increased implicit arousal in response to faces depicting negative but not positive emotional content after 7 days | ||||||||
| 2019 | Exploring ayahuasca-assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada | Indigenous members of a rural Coast Salish community in British Columbia (BC), Canada (19–56 y/o, mean 38 y/o, n = 11, 6 males and five females) | Observational naturalistic study | Ayahuasca | Ayahuasca (50–100 ml, twice over 2 days) | Some of the participants reported improved emotional openness at 6 months follow up Some of the participants improved their social relationships and had better communication with friends and family at 6 months follow-up | None reported | Argento et al. (2019) |
| 2020 | LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors | Healthy volunteers (male and female, 20 y/o to 40 y/o, average 25.25 y/o, n = 24, 18 males, 6 females) | Double blind, placebo controlled, within subjects | LSD ketanserin | LSD 100 μg, once, per oral solution ketanserin pretreatment (60 min prior) 40 mg, once, per oral solution | LSD increases the adaptation to the opinions of others if they are similar to one’s own LSD modulates neuronal activity in the mPFC during social feedback processing and not during social decision-making (blocked by ketanserine) |
No substantial side effects acutely and after 3 months Transient mild headaches (4 participants) after drug effects had worn off Transient sleep disturbances for the first two nights after drug administration (1 participant) |
Duerler et al. (2020) |
| The magnitude of LSD-induced social adaptation change is associated with personality Patients with higher neuroticism scores adapt more strongly after LSD administration LSD has the strongest impact on social cognition in patients with lower sociability and higher neuroticism scores at baseline | ||||||||
| 2021 | Role of the 5-HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin | Healthy volunteers (25–52 y/o, average age: 29 n = 16, 8 males, 8 females) | Double-blind, placeo-controlled, crossover design | LSD ketanserin | LSD 25, 50, 100, or 200 μg, once, per oral solution ketanserin 20 mg, once, per oral solution | LSD dose-dependently increased explicit and implicit emotional empathy LSD 200 µg significantly increased emotional empathy compared to placebo ketanserin did not significantly reduce the LSD-induced increase in empathy LSD increased blood oxytocin levels 1 and 3 h after drug intake, and this effect was blocked by ketanserin administration |
None reported | Holze, Avedisian, et al. (2021) |