Psychopharmacology
August 1, 2020
Theresa M Carbonaro, Matthew W Johnson, Roland R Griffiths
51 citations
Psilocybin produces stronger positive subjective effects than dextromethorphan (DXM) at comparable peak drug strength, which may explain its higher rates of non-medical use. In a double-blind study of 20 healthy participants with hallucinogen experience, psilocybin (10, 20, 30 mg/70 kg) and DXM (400 mg/70 kg) both increased ratings of overall drug effect, but psilocybin showed dose-related increases in nine domains linked to reinforcing effects—including liking, visual effects, positive mood, insight, social effects, appreciation of beauty, awe, meaningfulness, and mystical experience. For most ratings, the two highest psilocybin doses were significantly greater than DXM, and DXM never exceeded psilocybin. These differences matched participants' desire to take the drug again.
NeuroImage
October 15, 2022
Andrew Gaddis, Daniel E Lidstone, Mary Beth Nebel et al.
38 citations
Psilocybin alters the functional organization of distinct thalamic subregions and their connections to cortical networks, particularly the mediodorsal and pulvinar nuclei. Using a novel ICA-based approach in 18 healthy meditators, psilocybin-induced changes in intrathalamic spatial organization correlated with subjective drug effects. Thalamocortical connectivity predominantly decreased with visual and default mode networks. In contrast, treating the thalamus as a single unit showed a non-significant numerical increase in connectivity, suggesting that whole-thalamus analyses may mask focal decreases in specific nuclei that express serotonin 2A receptors.
Neuropharmacology
August 17, 2022
Jack E Henningfield, Marion A Coe, Roland R Griffiths et al.
34 citations
New medicines containing classic hallucinogenic and entactogenic psychedelics like psilocybin, LSD, and MDMA are being developed for psychiatric and neurological disorders. These substances are currently Schedule I under the US Controlled Substances Act (CSA) and similarly controlled globally. The CSA framework governs research, drug approval, and rescheduling; upon FDA approval, a drug containing a Schedule I substance must be rescheduled. Abuse potential research informs the eight CSA factors used for rescheduling, as well as product labeling and required risk evaluation and mitigation strategies (REMS). Standard human abuse potential studies are problematic for strong hallucinogens like psilocybin, so alternative strategies are discussed. Abuse-related research may also illuminate mechanisms of action, therapeutic effects, and effects on brain, behavior, mood, spirituality, and consciousness.
Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees
October 1, 2022
David B Yaden, Brian D Earp, Roland R Griffiths
31 citations
Psychedelics partly achieve their therapeutic effects through the subjective experiences they produce and how individuals interpret those experiences. Because these subjective effects can be disturbing for people with certain mental illnesses, researchers are developing 'nonsubjective' psychedelics that cause similar biological changes without the characteristic subjective effects. The authors broadly support creating such substances for scientific and clinical reasons but argue they should be reserved only for cases where subjective effects are specifically contraindicated. Classic psychedelics that produce subjective experiences should remain the default standard of care, as withholding typically positive, meaningful, and therapeutic experiences from most patients raises ethical concerns.
Current topics in behavioral neurosciences
January 1, 2022
David B Yaden, Sandeep M Nayak, Natalie Gukasyan et al.
31 citations
End-of-life and palliative care have improved, but psychopharmacological options for depression, existential distress, and well-being remain limited. This review examines recent clinical research on psychedelics for patients with life-threatening diagnoses and proposes that psychedelics could offer clinicians an additional treatment option in end-of-life and palliative care settings.
Current psychiatry reports
December 1, 2022
Natalie Gukasyan, Colleen C Schreyer, Roland R Griffiths et al.
29 citations
Psychedelic-assisted therapy (PAT) may be safe and effective for various mental health conditions, including eating disorders such as anorexia nervosa. Classic psychedelics could have transdiagnostic benefits through mechanisms relevant to eating disorder pathology. Interest in and efforts to increase access to PAT are high, but early clinical trials are focused on safety and utility, with efficacy remaining unclear. High-quality published data supporting PAT for eating disorders is lacking, though recent studies suggest it may augment current interventions for these difficult-to-treat conditions.
Drug and alcohol dependence
March 1, 2013
Lawrence P Carter, Chad J Reissig, Matthew W Johnson et al.
28 citations
Acute high doses of dextromethorphan (DXM) impair attention, working memory, episodic memory, and metacognition in healthy volunteers with histories of hallucinogen use. Impairments from 100–300 mg/70 kg DXM were generally smaller than those from 0.5 mg/70 kg triazolam. Doses needed to match triazolam's impairment exceeded 10–30 times the therapeutic dose. Supratherapeutic doses caused impairments on all tasks, indicating a broad therapeutic window for over-the-counter DXM when used appropriately, but relevance to high-dose abuse.
Psychological review
March 1, 2024
Manoj K Doss, Jason Samaha, Frederick S Barrett et al.
24 citations
Psychoactive drugs produce unique subjective states, but their effects on episodic memory often overlap. This reanalysis of 10 data sets (28 drug conditions) used signal detection models to separate three memory processes: recollection (retrieving specific details), familiarity (recognizing without details), and metamemory (introspecting about memory accuracy). Sedatives impaired both recollection and familiarity during encoding but enhanced recollection during consolidation. Dissociatives and cannabinoids impaired recollection during encoding, and cannabinoids increased false recollections during retrieval. Psychedelics impaired recollection during encoding but tended to enhance familiarity. Stimulants enhanced metamemory during encoding and retrieval but impaired metamemory during consolidation. These distinct patterns help explain drug-specific phenomena like sedative-induced blackouts and psychedelic presque vu, and suggest that memory quantity and stability influence metamemory.
Psychiatry Research
July 23, 2023
Otto Simonsson, Per Carlbring, Robin Carhart-Harris et al.
24 citations
In a meta-analysis of three psilocybin trials for depression involving 102 participants, clinically significant symptom worsening occurred for a minority of those receiving psilocybin or escitalopram (about 10%) and for a majority of those in the waitlist condition (63.6%). The psilocybin arm showed a lower likelihood of symptom worsening compared to waitlist and no difference compared to escitalopram. The authors note the limitation of a relatively small sample size.
JAMA psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
Journal of psychoactive drugs
January 1, 2023
Julian Urrutia, Brian T Anderson, Sean J Belouin et al.
21 citations
Combining psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems in integrative, community-based models of care could transform global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that positively affect health, well-being, and prosocial behavior, and combining them appears synergistic. Traditional knowledge systems offer ethnobotanical expertise and time-tested practices. A decolonized agenda for psychedelic research requires collaborative engagement with traditional knowledge stewards to co-develop evidence-based integrative care accessible to their communities. Health systems could include Indigenous and traditional healers as stakeholders in designing, implementing, and evaluating community-based approaches for safely scaling psychedelic treatments.
Psychopharmacology
March 1, 2013
Lawrence P Carter, Bethea A Kleykamp, Roland R Griffiths et al.
19 citations
Ketamine causes less cognitive impairment than triazolam at doses that produce greater subjective effects, and unlike triazolam, it does not lead to an underestimation of impairment. In a double-blind study with 20 healthy volunteers, ketamine impaired balance only when assessed early, while triazolam impaired psychomotor coordination and divided attention regardless of task order. Triazolam also tended to impair working memory and episodic memory more than ketamine at doses that produced lower subjective effects and higher performance estimates.
Journal of Psychoactive Drugs
May 7, 2024
Sandeep M Nayak, Sydney H White, Samantha N Hilbert et al.
18 citations
A prospective longitudinal study of 657 people planning a psilocybin experience outside a laboratory found that after the experience, participants reported increased perception of minds in various living and non-living entities such as plants and rocks, replicating earlier findings. However, the study found little to no change in participants' metaphysical beliefs, such as dualism, or in their self-reported Atheist-Believer status. These results contrast with cross-sectional studies suggesting psilocybin experiences alter Atheist-Believer status and non-naturalistic beliefs, but they support the relevance of mind perception and mentalization processes.
Journal of psychopharmacology (Oxford, England)
April 1, 2016
Matthew W Johnson, Katherine A Maclean, Michael J Caspers et al.
11 citations
After inhaling a high dose of vaporized salvinorin A (18–21 mcg/kg), plasma levels of the compound peak at 2 minutes and then rapidly decline. Higher drug levels are strongly linked to stronger subjective and observer-rated drug effects. Prolactin rises significantly from 5 minutes onward, peaking at 15 minutes, while cortisol increases are inconsistent across participants. Hormonal changes do not closely track drug levels. This work demonstrates a direct relationship between salvinorin A plasma concentrations and drug effects in humans, validating an efficient inhalation method.
Journal of psychoactive drugs
February 13, 2025
Yitong Xin, Roland R Griffiths, Alan K Davis
1 citation
Among ayahuasca users who report encountering an entity during their experience, males and females show different patterns of religious belief change. Before the encounter, males were more likely to identify as atheists and less likely to hold religious beliefs than females. After the encounter, both sexes became less atheist or agnostic and more religious, but the shift was larger for males: the proportion of religious males rose significantly, while the increase for females was not statistically significant. These results suggest that sex is linked to how religious beliefs shift after an entity encounter, pointing to the importance of considering sex in psychedelic research on spirituality.