{"doi":"10.1002/cpt.3050","title":"Psychedelics and Psychotherapy: Is the Whole Greater than the Sum of its Parts?","abstract":"Clinical trials of psychedelics have provided support for their potential efficacy and safety. Although most combined a psychedelic with psychological support akin to psychotherapy, providing psychotherapy is costlier and more difficult to scale than providing only support to reduce harms. Trials with factorial designs can evaluate the individual effects of a psychedelic and psychotherapy and any synergistic interaction between them. Such trials would provide an important evidence base for developing safe and cost-effective psychedelic treatments. Psychedelics, such as psilocybin, have received increasing attention over the past 2 decades as potential treatments for a variety of medical conditions, including depression, anxiety disorders, chronic pain, and migraine and cluster headache.1-5 This is undoubtedly a result of several factors, including promising results of early clinical trials, generally modest efficacy of existing treatments for these conditions, and provocative reports in the popular press. Despite this enthusiasm, critically important questions about psychedelics remain unanswered, especially confirmation of efficacy and safety in phase III trials as well as mechanisms of action, appropriate contexts of use, and methodologic challenges, including blinding integrity.3-5 In addition, future clinical trials will need to examine the potential roles of postdosing neuroplasticity from psychedelics6 and of home and other environmental factors7 in accounting for whether treatment benefits persist. In these comments, we focus on “classic” psychedelics administered as single doses that typically cause marked perceptual effects and alterations in consciousness (e.g., psilocybin, mescaline, and LSD) primarily via serotonin 2a agonism. These are distinct in mechanism from other agents with somewhat similar subjective effects (e.g., ketamine and MDMA). However, many of the issues we discuss are applicable to these other medications as well as to “microdosing.”1 Clinical trials of classic psychedelics conducted during the past 2 decades have typically randomized patients to 1 or 2 doses of a psychedelic vs. an inert placebo or other treatment intended to make it more likely that patients and investigators will remain blinded to the treatment allocation (e.g., a stimulant, sedative-hypnotic, or lower psychedelic dose).3 In most of these trials, patients also received some type of psychotherapy or supportive counseling, with preparatory visits that began before the psychedelic was administered and that often continued for several weeks thereafter. The specific type of psychosocial support provided has been heterogeneous, including cognitive-behavioral, supportive, and motivational therapies. Although we acknowledge there can be debate about the precise nature of the psychological interventions offered in psychedelic trials,2 we argue that these frequently share such factors common to all psychotherapies as the importance of the therapeutic relationship, the healing setting, and an overarching therapeutic rationale.8 Thus, for the purposes of this paper, we refer to these psychological interventions as psychotherapy. Several different assumptions have been made about the benefits of combining psychedelics with support or therapy. Foremost among these is safety; even in the controlled environment of clinical trials, for some individuals, psychedelic experiences can be frightening, including anxiety, hallucinations, and paranoia.1 In addition, adverse cardiovascular events have been reported in individuals taking classic psychedelics.5 For these reasons, careful preparation of patients enrolled in clinical trials and the presence of trained monitors during the psychedelic session are considered essential to minimize harms.5 Many investigators also believe that providing psychotherapy in combination with a psychedelic enhances the magnitude and duration of the benefits of the psychedelic. For this reason, preparatory psychotherapy ","journal":"Clinical Pharmacology & Therapeutics","year":2023,"id":340256,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":317519,"name":"Michael McDermott","orcid":"0000-0002-1015-0745","position":1,"is_corresponding":false},{"id":659819,"name":"Sandeep M. Nayak","orcid":"0000-0002-6832-0639","position":2,"is_corresponding":false},{"id":492543,"name":"Eric C. Strain","orcid":"0000-0001-8482-5461","position":3,"is_corresponding":false},{"id":250019,"name":"Robert H. Dworkin","orcid":"0000-0002-9464-5488","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T01:10:54.145367Z","pmid":"37795632","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}