Classic hallucinogens in the treatment of addictions

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Highlights

  • We review the use of classic hallucinogens in the treatment of addiction.

  • Controlled trials support the efficacy of high-dose LSD for alcoholism.

  • Pilot studies of psilocybin for nicotine and alcohol dependence suggested benefit.

  • Definitive studies of efficacy and therapeutic mechanisms remain to be done.

Abstract

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.

Introduction

The purpose of this paper is to provide a review and discussion of the scientific literature pertaining to the use of classic hallucinogens in the treatment of addiction. After highlighting the urgent need for new treatments for addiction, we provide background on the history of research on hallucinogens, a brief review of the biological and psychological effects of classic hallucinogens, and a description of the specific classic hallucinogens that have been studied in relation to addiction treatment. We then provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review existing research on possible therapeutic mechanisms of action concerning hallucinogens, and suggest directions for future research on the use of classic hallucinogens in the treatment of addiction.

Section snippets

The public health impact of addictions

Addictive disorders are very common, with lifetime prevalence rates in the US population estimated at 25% for nicotine use disorder (Hughes et al., 2006), 12% for alcohol use disorder (Hasin et al., 2007), and 10.3% for illicit drug use disorder (Compton et al., 2007). Addiction to alcohol, tobacco, and other drugs is the leading preventable cause of death and disability in the United States and globally (Rehm et al., 2006). Tobacco smoking alone causes 5 million deaths annually, including

LSD

In the 1950s through early 1970s over 30 publications reported on the effects of LSD in the treatment of alcoholism (for reviews see Abuzzahab and Anderson, 1971, Halpern, 1996, Mangini, 1998, Dyck, 2006, Grinspoon and Balakar, 1997). Early reports of clinical outcomes and uncontrolled trials had variable but encouraging results, particularly when the psychedelic model was used (Abuzzahab and Anderson, 1971). At least a dozen trials with some form of control group were ultimately conducted (

Supportive non-experimental data from religious and clinical contexts

Although ayahuasca and peyote have not been subjected to clinical trials, they are of interest because they contain classic hallucinogen compounds, and they have been and continue to be used extensively outside of clinical research, including current use with the intent of curtailing addiction. We briefly summarize the most relevant non-experimental research on these substances below.

Possible mechanisms of action

Since there are very few studies directly investigating the role of specific effects of classic hallucinogens in subsequent change in addictive behavior, this section is necessarily speculative. Still, we feel it is important to identify plausible mechanisms of action at the current early stage of investigation in order to generate hypotheses for future research. There are several known actions of classic hallucinogens that are related to mechanisms of addiction, and could possibly mediate

Safety

The potential for classic hallucinogens in addiction treatment requires an understanding of risks and safety mechanisms to minimize potential harms. A broad exploration of risks and proposed safety issues has been previously described (Johnson et al., 2008). However, a brief description will be provided here.

Conclusions/future directions

Taken as a whole, the evidence suggests that classic hallucinogens hold considerable promise in the treatment of addiction, particularly given the limited efficacy of extant treatments. The efficacy data are promising, but very limited except in the case of LSD treatment of alcoholism. Trials are only now beginning that will meet modern standards of design and statistical power. Classic hallucinogens have several features that one might want a priori in an anti-addiction drug. 1) They lack

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