Editorial: Psychedelics as treatments for substance use disorders: exploring therapeutic potential, risks, underlying mechanisms of action, and implementation challenges

Psychedelics may offer new treatments for substance use disorders (SUDs), which cause high rates of illness and death. Current treatments often fail: in one trial, 57% of patients on buprenorphine and 65% on naltrexone relapsed by 24 weeks, and 40% leave 12-step groups within a year. This special issue presents seven articles exploring psychedelics' potential for SUDs, including psilocybin for methamphetamine use disorder and ketamine's effects on brain plasticity. One review found mixed evidence for ketamine's impact on synaptic markers in the hippocampus and prefrontal cortex. A perspective piece argues for equitable access to psychedelic therapies, including training diverse clinicians and serving higher-risk patients.

Study at a glance

Abstract

Disclosures of Financial or Other Potential Conflicts of Interest: Dr. Barnett holds stock options in CB Therapeutics. He also serves on advisory boards for CB Therapeutics and Compass Pathways. He receives monetary compensation from DynaMed Plus (EBSCO Industries, Inc.) for editorial work and from Janssen Pharmaceuticals for consulting services. Dr. Barnett has received research funding from MindMed. Dr. Sackett acts as a consultant to Resa-Health. The other authors declare no conflicts of interest.Though relatively under-researched compared to mood and anxiety disorders, the therapeutic applications of psychedelics for substance use disorders (SUDs) represent important possibilities for treating conditions that inflict tremendous morbidity and mortality. In recent decades, growing rates of mental illness 1 and social isolation 2 have intersected with increasingly efficient technologies in the processing, manufacturing, and dissemination of psychoactive substances to greatly exacerbate the prevalence and harms of SUDs. While psychotherapy, mutual support groups, and pharmacological interventions are effective for some with these conditions, for too many they prove inadequate means for ensuring long term recovery. For example, in an open label trial of sublingual buprenorphine versus monthly-administered extended release naltrexone in opioid use disorder, at 24 weeks 57% and 65% of patients had relapsed, respectively. 3 Other studies have identified a 40% attrition rate from 12-step recovery groups within the first year of joining 4 and a 30% attrition rate for psychosocial SUD treatments in general. 5 Numbers like these clearly indicate that novel approaches to treating SUDs are needed-could psychedelics help fill the gap?In this special issue, we present seven articles exploring the therapeutic potential of classic and non-classic psychedelics for SUDs. Recognizing that psychedelic research has been prone to hype 6 and that unique questions related to potential therapeutic applications of psychedelics in patients with SUDs (such as psychedelics' addictive potential in this population) remain open, we sought to curate an article collection providing a balanced take on the current state of knowledge for this exciting, though sometimes controversial topic. data were only reported for less than a week. Lorcaserin is not a psychedelic, though 5-HT2c agonism may play a role in psychedelics' potential anti-addictive properties, since this modulates dopaminergic activity in the ventral tegmental area-nucleus accumbens reward pathway. 7 Rounding out articles on human data, Brett and coauthors present a mini-review on psilocybin-assisted therapy for methamphetamine use disorder (MUD), a condition for which current pharmacological treatments offer little to no efficacy, and discuss the rationale for investigating psilocybin-assisted therapy for this indication. The authors note that since psilocybin-assisted therapy has demonstrated promising findings in clinical trials for AUD and tobacco use disorder, the possibility of transdiagnostic treatment potential justifies exploring its potential in MUD.Zhornitsky and coauthors explore the potential of neuroplasticity as a therapeutic mechanism for psychedelics in patients with SUDs, as well as mental health conditions, by systematically reviewing the effects of psychedelics on markers associated with synaptic density. They found most eligible studies have investigated the non-classic psychedelic ketamine, with mixed findings for synaptic changes in the hippocampus and prefrontal cortex when ketamine is administered in single or repeated doses. Fewer studies have been conducted for other psychedelics, though these data indicate that markers associated with synaptic density can be enhanced under basal conditions and that stress-associated deficits can be reversed. Taken together, these findings suggest that psychedelics' abilities to normalize abnormal levels of synaptic markers in some brain regions could contribute to their treatment potential for SUDs.Finally, in a compelling perspective piece, Black argues for an increased focus on the potential of psychedelic treatments for patients with SUDs. To do this demands that we work towards equitably employing psychedelic therapies, rather than maintaining the status quo in mental healthcare, which would likely see them primarily restricted to use in wellness markets or patients who are commercially insured. Among other points, Black observes that recruitment and training of diverse psychedelic clinicians, collaboration with mutual support groups, and a willingness to provide access to psychedelic treatments to higher-risk individuals in need of complex care will be essential to maximizing the potential societal benefits of psychedelic assisted therapy. In summary, these articles provide a valuable view into the emerging field of psychedelics as potential treatment for SUDs. With growing interest among researchers in exploring this line of inquiry, we expect this collection will prepare readers for deeper future engagement with an area of research that could yield important assistance in humanity's quest to ameliorate the widespread suffering wrought by SUDs.