Pharmacology & therapeutics
May 1, 2019
Matthew W Johnson, Peter S Hendricks, Frederick S Barrett et al.
520 citations
Classic psychedelics like LSD, mescaline, and psilocybin are serotonin 2A receptor agonists with a long history of sacramental use and a resurgence in research. Epidemiological studies suggest naturalistic nonmedical use may be linked to positive mental health and prosocial outcomes, though some individuals are harmed in unsupervised settings. Recent therapeutic studies indicate efficacy in treating psychological distress from life-threatening diseases, depression, and nicotine and alcohol addictions. These compounds fairly reliably occasion mystical experiences, which are associated with improved psychological outcomes in healthy volunteers and patients. Neuroimaging studies reveal neurobiological mechanisms, broadening understanding of the brain, serotonin system, and consciousness. Overall, classic psychedelics show strong therapeutic potential and as tools for investigating mystical experiences and brain function.
Pharmacology & therapeutics
May 1, 2004
John H Halpern
209 citations
Many hallucinogens and dissociative agents can be obtained from plants and fungi growing wild or in gardens across the United States, contrary to the common belief that such drugs are only smuggled or clandestinely produced. This article reviews botanical sources containing N,N-dimethyltryptamine, MAOIs, lysergic acid amide, anticholinergic drugs, salvinorin-A, mescaline cacti, psilocybin mushrooms, and Amanita muscaria and Amanita pantherina. Dangerous misidentification is most common with mushrooms, but a novice forager can learn to properly identify and prepare many of these plants. The article covers geographical range, drug content, preparation, intoxication, health risks, and the legal protections sought by religions like the Santo Daime and Uniao do Vegetal for sacramental ayahuasca.
Pharmacology & therapeutics
May 1, 2004
Bryan L Roth, Estela Lopez, Scott Beischel et al.
98 citations
Psychoactive plants alter perception, emotion, and cognition, and understanding their molecular mechanisms may reveal the biological basis of consciousness and provide validated targets for central nervous system drug discovery. This review describes an unbiased, discovery-based approach that screens the main active ingredients of psychoactive plants against the 'receptorome'—the portion of the proteome encoding receptors. It overviews the receptorome, describes public-domain in silico resources, and details new tools for mining data from the National Institute of Mental Health Psychoactive Drug Screening Program's K(i) Database. Three case studies on Hypericum perforatum, Salvia divinorum, and Ephedra sinica illustrate the approach, and recommendations for future studies are offered.
Pharmacology & therapeutics
February 1, 2018
Laura Hondebrink, Anne Zwartsen, Remco H S Westerink
78 citations
More than 600 new psychoactive substances (NPS) have been reported, yet information on their neuropharmacological and toxicological effects remains limited, hampering risk assessment. A review of in vitro neuronal modes of action created effect fingerprints for frequently reported NPS classes: cathinones, cannabinoids, hallucinogenic phenethylamines, arylcyclohexylamines, and piperazine derivatives. The fingerprints highlight main modes of action—such as inhibition or reversal of monoamine reuptake transporters for cathinones and activation of 5-HT2 receptors for hallucinogenic phenethylamines—and identify additional targets, including dopamine, adrenergic, GABAA, and acetylcholine receptors, by relating effect concentrations to estimated...
Pharmacology & therapeutics
November 1, 2022
Sanket B Raut, Padmaja A Marathe, Liza Van Eijk et al.
62 citations
PTSD is a chronic condition marked by abnormally persistent and distressing memories, with current treatments limited to psychotherapy and two FDA-approved drugs that reduce depression and anxiety but do not produce permanent remission. Early evidence suggests psychedelics like psilocybin, MDMA, LSD, cannabinoids, ayahuasca, and ketamine, especially combined with psychotherapy, may help by increasing trust and enabling modification of trauma-related memories. Research into memory reconsolidation has identified pharmacological targets to disrupt fear memories. Pre-clinical and clinical studies have investigated novel agents such as neuropeptide Y, oxytocin, cannabinoids, and neuroactive steroids. While many drugs show promise in pilot trials, large-scale clinical trials are needed for clinical adoption.
Pharmacology & therapeutics
August 1, 2023
Ryoichi Fujiwara, Megan Journey, Fatimah Al-Doori et al.
13 citations
New psychoactive substances (NPSs) such as synthetic cannabinoids, synthetic cathinones, phenethylamines, and piperazines are often falsely marketed as natural and safe but cause severe adverse effects including seizures, nephrotoxicity, and death. Their use has risen sharply among adolescents and young adults due to low cost and easy availability. As of January 2020, nearly 1000 NPSs have been documented. Use of NPSs is linked to higher rates of unplanned pregnancy; about 4 in 100 women in substance abuse treatment are pregnant or nursing.
Pharmacology & therapeutics
February 1, 2004
David E Nichols
1 citation
Hallucinogens (psychedelics) powerfully alter perception, mood, and cognition, are physiologically safe, and do not cause dependence. Their use predates written history in ritual contexts. Early research linked LSD to serotonin (5-HT), and it is now known that hallucinogens stimulate 5-HT(2A) receptors on neocortical pyramidal cells, increasing cortical glutamate. These effects are compared to acute psychosis, with thalamocortical interactions key to altered states of consciousness. Brain imaging shows increased prefrontal cortical metabolism. The 5-HT(2A) receptor is essential for cognitive processing, and its ligands may aid cognitive neuroscience. Hallucinogens may also have therapeutic utility for alcoholism, substance abuse, and psychiatric disorders.