Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent v...
Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problemati...
The beneficial effects of psilocybin-assisted psychotherapy on alcohol use disorder (AUD) are significant, based on a study published in JAMA Psychiatry last month. In general, psychedelic medications have been a focus of research, but less is known about psilocybin, and it has been 40 years since the studies with lysergic acid diethylamide (LSD) provided do...
IntroductionAlcohol use disorder is a difficult-to-treat psychiatric disorder and a major burden on public health. Existing treatment efficacy is moderate, and relapse rates are high. Preliminary findings suggest that psilocybin, a psychedelic compound, can safely and reliably occasion highly meaningful experiences that may spur a positive change in drinking...
IntroductionMescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, res...
ImportanceAlthough classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.ObjectiveTo evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with a...
Hallucinogen persisting perception disorder (HPPD) is characterized by visual disturbances that resemble psychedelic intoxication and linger after use has ceased. The most common substances precipitating HPPD, lysergic acid diethylamide (LSD) and psilocybin, are posited to do so via damage to serotonergic neurons involved in vision. Mr. N is a 37-year-old wi...
Existing pharmacological treatments for psychiatric disorders have demonstrated limited efficacy, delayed onset of action, and significant burden of side effects. Recent findings from human studies with psychedelics have shown promise, demonstrating rapid and sustained clinical benefits of these compounds for a variety of psychiatric disorders. Classical psy...
With nicotine being one of the most addictive substances and the available treatments for nicotine addiction leading to no better than a 30% success rate, it's no wonder that a newly announced multisite study of the psychedelic psilocybin for smoking cessation is generating excitement. While taking care not to oversell the potential of this strategy, those i...
Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood, and new effective pharmacological treatments are desired. Here, using a bidirectional neuromodulation approach, we demonstrate a ca...
The past decade has witnessed a rapid growth of research on the basic science and clinical understanding of psychedelics. This chapter provides an overview of the human behavioral pharmacology of psychedelics focusing on three prototypic classic psychedelics-psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT). A brief historical overvi...
First it was the plant, cannabis. How could this be made into a saleable profit-making commodity when it grows in the ground? Witness the marijuana (a chemical from the plant) industry, which lobbied to make sure laws in states that legalized it banned people from growing more than a few plants.
Several pilot studies have provided evidence supporting the potential of classic psychedelics like psilocybin in the treatment of substance use disorders (SUDs). If larger trials confirm efficacy, classic psychedelic-assisted psychotherapy may eventually be integrated into existing addiction treatments such as cognitive behavioral therapy, contingency manage...
Psychedelics are a hallucinogenic class of psychoactive drugs with the primary effect of activating non-ordinary states of consciousness. Due to the positive preliminary findings of these drugs in the treatment of psychiatric disorders, the number of registered clinical studies has risen significantly. In this paper, clinical studies registered on clinicaltr...
ObjectiveTo conduct a systematic review of modern-era (post-millennium) clinical studies assessing the therapeutic effects of serotonergic psychedelics drugs for mental health conditions. Although the main focus was on efficacy and safety, study characteristics, duration of antidepressants effects across studies, and the role of the subjective drug experienc...
This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinica...
The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorder...
Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder bein...
Antidepressant, atypical antipsychotic, and hallucinogen drugs mediate their actions in part by interactions with the serotonin-2A (5HT2A) receptor. Serotonergic hallucinogen drugs, such as psilocybin, bind most potently as agonists at the 5HT2A receptor, producing profound changes in perception, mood, and cognition. Some of these drugs have been or are curr...
