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5 Classic Hallucinogens Studied in the Treatment of Addictions
Michael P. Bogenschutz, MD
This slideshow provides information about the compounds, clinically relevant attributes, approximate dose, and data under study.
Evidence suggests that classic hallucinogens may hold considerable promise in the treatment of substance use disorders, particularly given the unique mechanisms of these drugs, their low toxicity, the potential to induce lasting change after a few administrations (or even one) of the drug, and the limited efficacy of existing treatments. This slideshow provides information about the compounds, clinically relevant attributes, approximate dose, and data that have been studied in relation to substance use disorders. For more on this topic, see Innovative Strategies for Addressing Substance Use Disorders: The Classic Hallucinogens, on which this slideshow is based.
Teaching point: Although the preliminary efficacy data are suggestive, it must be underscored that they are very limited except in the case of LSD treatment of alcoholism.
Approximate dose: 100-800 mg orally
Trials for other indications: pain, existential anxiety and depression. Completed or ongoing trials: Alcohol use disorder, Opioid use disorder
Teaching point: Based on existing evidence, none of the classic hallucinogens meets medical standards for safety and efficacy. Large rigorous trials will need to be completed to determine whether classic hallucinogens have a place in the treatment of addiction or other psychiatric disorders.
Centuries of use in traditional religions/shamanic contexts; trials for other indications: existential anxiety and depression, obsessive-compulsive disorder, major depression.
Approximate dose: 10 mg to 40 mg orally
Completed or ongoing trials: Alcohol use disorder, Nicotine use disorder, Cocaine use disorder
Teaching point: Considerable data support the safety of these drugs when patients are carefully screened and prepared, and appropriate safeguards are employed. Thus, there do not appear to be valid scientific or ethical barriers to energetically addressing questions of efficacy, which were prematurely dropped over 40 years ago.
Approximate dose: 15 mg to 165 mg IM
Completed or ongoing trials: Alcohol use disorder
Teaching point: 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.
Over 5000 years of use in traditional religious/shamanic contexts; effects similar to those of LSD; used interchangeably with LSD in early psychedelic treatment
Approximate dose: 200 mg to 500 mg orally
Completed or ongoing trials: Alcohol use disorder
Teaching points: 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).
Centuries of use in traditional religious contexts; current clinical (where allowed) and underground (where illegal) use of ayahuasca for addictions and other conditions.
Approximate dose: 0.5 mg/kg to 1.76 mg/kg orally in ayahuasca; 0.1 mg to 0.4 mg/kg IV; or 25 mg smoked
Completed or ongoing trials: Alcohol use disorder