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Innovative Strategies for Addressing Substance Use Disorders: The Classic Hallucinogens: Page 2 of 5

Innovative Strategies for Addressing Substance Use Disorders: The Classic Hallucinogens: Page 2 of 5

Table – Classic hallucinogens studied in the treatment of addictionsTable – Classic hallucinogens studied in the treatment of addictions

This article summarizes and discusses the scientific evidence relevant to the use of classic hallucinogens in the treatment of substance use disorders. Although none of these compounds is approved for clinical use, interest in the therapeutic potential of these drugs has increased steadily, particularly in the past decade. Recent early-stage trials of psilocybin in the treatment of alcohol and tobacco use disorders, as well as for anxiety and depression in the context of a life-threatening cancer diagnosis, have had very promising results.

The lay press and the Internet have featured many reports of beneficial effects of classic hallucinogens—sometimes exaggerating the possible benefits and minimizing the risks of these drugs. On the other hand, some clinicians and scientists still have an exaggerated view of the risks of classic hallucinogens and reject consideration of their possible clinical value, perhaps because of the reputation of classic hallucinogens as drugs of abuse, or owing to a lack of familiarity with both recent and older literature on their therapeutic use. It is hoped that this article contributes to a more fully evidence-based discussion of the possible clinical value, as well as the risks, of these compounds.

Substance misuse is the leading preventable cause of death and disability in the world.1 The economic costs of substance use disorders—including factors such as health care costs, lost productivity, crime, incarceration, and law enforcement—are estimated at over half a trillion dollars per year in the US alone. Although effective behavioral and pharmacological therapies exist, currently available treatments help only a minority of those who are treated. For example, approximately 1 person achieves abstinence or avoids relapse for every 9 persons treated with the most effective FDA-approved pharmacotherapies for alcohol use disorder.2,3 With approved medications for smoking cessation, fewer than 35% of those treated remain smoke-free 6 months after treatment.4 Most medications for substance use disorders require adherence to treatment for relatively long periods, which further limits their effectiveness.

Classic hallucinogens

The term “hallucinogen” includes a wide variety of drugs with several different mechanisms of action and widely varied effects, of which actual hallucinations are a relatively minor part. Although there is some overlap in the effects of the various classes of hallucinogens, the risks and possible benefits vary greatly among these drugs.

The main focus of this article is classic hallucinogens. This class of drugs is thought to act primarily as agonists or partial agonists at the serotonin 2A (5-HT2A) receptor. There are 2 structural classes of classic hallucinogens: the indoleamines and the phenylalkylamines. The indoleamines share structural similarities to serotonin and include dimethyltryptamine (DMT), psilocin (4-hydroxy-DMT), psilocybin (4-phosphoryloxy-DMT), N,N-dipropyltryptamine (DPT), and lysergic acid diethylamide (LSD). The phenylalkylamines comprise mescaline and synthetic hallucinogens, including substituted amphetamines such as dimethoxymethylamphetamine (DOM). The Table provides information about the classic hallucinogens that have been studied in relation to substance use disorders.

The acute effects of all the classic hallucinogens are similar but vary in duration and intensity depending on the particular substance, dose, and route of administration. Physiological toxicity is very low with the doses of LSD, psilocybin, mescaline, DPT, and DMT that are typically used in clinical research. Pulse and blood pressure may be moderately elevated. Visual perception is often profoundly altered, and vivid imagery is frequently seen when the eyes are closed. Other sense modalities may be affected as well.

The sense of time is often distorted. Effects on emotion are extremely variable, and emotions can fluctuate rapidly and frequently during a single treatment session. Strong cathartic emotional experiences are common. The psychological content and emotional tone of the experience are unpredictable but are thought to be influenced strongly by the mental state, preparation, and intention of the person taking the drug; the environment in which the effects are experienced; the dose; and the particular drug that is taken. The content of the experience may be dominated by personal experiences and concerns, dream-like symbolic sequences, or religious or spiritual matters.


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