Substance use disorders (SUDs) are defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as having a minimum of two of eleven symptoms for at least 12 months. SUD symptoms are categorized by drug-seeking actions, behavioral consequences (e.g., risky drug use, impact on social or occupational functioning), physiological dependence (e.g., tolerance, withdrawal), psychological dependence (e.g., cravings), and time spent acquiring, using, or recuperating from the substances (American Psychiatric Association, 2013). The severity of SUDs ranges from mild to severe, depending on the number of symptoms endorsed. Importantly, the nomenclature has been modified with DMS-5, such that previous iterations differentiated between abuse (or misuse) and dependence (Substance Abuse & Mental Health Services Administration, 2016). Substance abuse or misuse refers to taking substances in a way that is risky and could cause harm to the individual or another person. By contrast, dependence refers to the physiological or psychological reaction to the absence of a drug. While SUD diagnoses no longer distinguish between misuse or dependence, these definitions are used in the text below to maintain consistency with the operational definitions of research that was conducted prior to DSM-5.
SUDs are prevalent, chronic conditions that are poorly treated due to both low treatment engagement and barriers to accessible and effective care. In fact, it has been estimated that nearly one in five Americans over the age of 12 meet criteria for an SUD, with alcohol (10.2 %), nicotine (8.0 %), and cannabis use (6.8 %) being the most common (Substance Abuse & Mental Health Services Administration, 2024). Of those diagnosed with an SUD, only 35–54 % of individuals achieved remission within 17 years of being diagnosed (Fleury et al., 2016). Despite the prevalence and chronicity of SUDs, only a quarter of those diagnosed have received treatment (Substance Abuse & Mental Health Services Administration, 2024). Low treatment rates are believed to reflect various individual, interpersonal, and system-level barriers, including perceptions that treatment is unwarranted, social stigma, poor therapeutic relationships with treatment providers, and a lack of available services or appropriately trained providers (see Farhoudian et al., 2022). Of those who receive treatment, it is estimated that only up to one-third attain abstinence by the end of treatment (Dutra et al., 2008, Henssler et al., 2021, Mottillo et al., 2009), highlighting the need to improve upon existing treatments.
Given the need for more accessible and effective treatment for SUDs, the current chapter evaluates the potential for psychedelics to treat SUDs. Psychedelics are often categorized into classic and atypical subsets. Classic psychedelics primarily exert their effects through serotonergic 2A receptor agonism. The most common examples of classic psychedelics include psilocybin, lysergic acid diethylamide (LSD), mescaline (derived from the peyote cactus), and dimethyltryptamine (DMT; active substrate in ayahuasca). By contrast, atypical psychedelics act on different neurotransmitters systems and include ibogaine, ketamine, and 3,4-Methylenedioxy methamphetamine (MDMA). While these atypical compounds have been historically identified as psychedelics, they will not be included in the current review due to their different pharmacological profiles, and reviews of these in substance use treatment can be found elsewhere (Mendes et al., 2022, Mosca et al., 2023, Walsh et al., 2022).
To date, there is empirical evidence on using classic psychedelics to treat five categories of SUDs: alcohol, tobacco, opioid, stimulant, and cannabis. While the field is still in its early stages, the most compelling evidence has been collected for alcohol use disorder, which includes evidence from multiple double-blinded randomized controlled trials. Tobacco and opioid use disorders also use interventional methods, but with some methodological limitations. By contrast, stimulant and cannabis use disorders are restricted to observational studies. As such, the state of the evidence varies greatly across SUDs. This chapter therefore provides a separate summary of the literature for each type of SUD. Next, potential mechanisms underlying the efficacy of psychedelics for SUD are proposed; followed by general overview of the limitations and proposed future directions for the field of psychedelics and SUD treatment.
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