Research from 2016 assessed the use of psilocybin in helping 15 individuals quit smoking. The findings indicated that two moderate doses of 200 micrograms decreased anxiety, with these effects persisting throughout a 12-month follow-up period. The results suggested that psilocybin produced a substantial and long lasting reduction in depression and anxiety, as well as increases in optimism and quality of life.

Effects of Psychedelic Drugs

• With adequate inclusion and exclusion criteria and clinical supervision, adverse physiological reactions are minimal (Malleson, 1971; Muttoni et al., 2019).
• More studies are needed to better understand how psychedelic and dissociative drugs work.
• A 26-year-old woman who attended the same party accidentally took around 500 micrograms of LSD but didn’t require medical intervention.15

More studies are needed to better understand how psychedelic and dissociative drugs work. For more information, see “How do psychedelic and dissociative drugs work in the brain? Other drugs such as MDMA, ibogaine, and salvia work on a variety of brain functions to cause psychedelic or dissociative effects.

However, some hallucinogenic drugs may lead to tolerance and some people report experiencing withdrawal effects when they stop using such substances. NIDA conducts and supports research to better understand how often and to what extent people experience tolerance, withdrawal, and other substance use disorder symptoms related to the use of psychedelic and dissociative drugs. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)—a reference text professionals use to diagnose substance use disorders and other psychiatric disorders—includes diagnoses of phencyclidine (PCP) use disorder and “other hallucinogen use disorder”64,65 but does not include substance use disorder diagnoses related to other specific psychedelic and dissociative drugs. Researchers are also studying whether some of these substances may be effective treatments for mental health disorders, including addiction, when administered in a clinical setting.4,5

Tolerance – the decreased response with repeated administration of a drug – has been reported to develop rapidly to the euphoric and psychedelic effects of hallucinogens but not to the autonomic effects, such as pupillary dilation, hyperreflexia, increased blood pressure (BP), increased body temperature, piloerection and tachycardia. This has been corroborated by studies in both humans and animals, where psychedelics show minimal reinforcing effects, meaning users are unlikely to develop cravings or physical withdrawal symptoms. Interestingly, psychedelics such as psilocybin (found in magic mushrooms) and LSD were placed at the lower end of the harm spectrum, indicating that they pose less risk than many commonly used substances, including alcohol and tobacco. A study published in Psychopharmacology in 2018 examined the potential for abuse and dependence among classic psychedelics, including LSD, psilocybin, and mescaline. And yet, for people who may have an underlying psychiatric comorbidity like schizophrenia or a bipolar disorder diagnosis, psychedelics might pose a serious health risk, said Mash. If someone has a substance-use disorder and it’s early, no one is recommending or suggesting that you should go ahead and try the psychedelics first as a method of treatment.”

• In comparison with other psychoactive drugs, psychedelics score consistently low in their abuse potential (Fábregas et al., 2010).
• One of the most notable findings from Nutt’s study is that psychedelics such as psilocybin and LSD have a low physical toxicity profile.
• Understanding the specific circumstances and individuals in which psychedelics may lead to challenging experiences will have important implications for future clinical research and harm reduction strategies.
• We exclude n-BOMEs, 3,4-methylenedioxymethamphetamine (MDMA), ketamine and ibogaine, as these are distinguished from classic psychedelics, both in their effects and in their pharmacology.

Why Do People Use Hallucinogens?

HUD is described in DSM-V as a problematic pattern of hallucinogen use (other than phenylcyclohexyl piperidine; PCP) leading to clinically significant impairment or distress. In addition to the traditional contexts, by now there is a large amount of anecdotal evidence of Western individuals having healed their depression, anxiety, addiction, PTSD and other trauma, and more through ayahuasca (e.g. Grob et al., 1996), highlighting the importance of further studying these promising effects scientifically. The first RCT comparing psilocybin to a conventional selective serotonin reuptake inhibitor (SSRI) antidepressant found the former to be as efficient at reducing symptoms of depression, and with fewer side effects (Carhart-Harris et al., 2021). Once LSD was banned, most countries made other serotonergic psychedelics illegal as well (Nutt et al., 2013; Rucker et al., 2018). Although studies were small, they reported largely positive effects and a lack of adverse effects (as reported by the clinician).

Adverse effects of psychedelics: From anecdotes and misinformation to systematic science

“I can say that while psychedelics helped me to stop using substances, I’d like to reflect that these aren’t a cure,” said Guckel, a founder of a company that offers psychedelic-assisted recovery. Now a professional recovery coach, Guckel said psychedelics might hold a promise to treat addiction disorders. Learn more about psychedelic and dissociative drugs and their legal status in the United States from the DEA. Information on the use of psychedelic and dissociative drugs is collected by several national surveys. Some organizations are using harm reduction practices to help avoid drug overdose deaths related to possible adulteration of certain psychedelic and dissociative drugs, particularly those taken in pill, powder, or liquid form.15 This means adulteration of psychedelic and dissociative drugs with fentanyl and similar compounds is possible, but more research is needed to understand to what extent this occurs.

Ayahuasca

While researchers debate how to describe these drugs and how specific drugs should be classified, they generally group them according to what is known about how they work in the brain. These drugs can make people feel disconnected from their body and environment.6 Many psychedelic drugs derive from plants and fungi, and some have been used for thousands of years in traditional or religious rituals. As psychedelics can produce euphoria and a feeling of detachment from the surroundings, some people use them recreationally to reduce feelings of stress. Some psychedelics, such as LSD, can cause tolerance, which can increase the risk of an overdose and potentially cause death.

Psilocybin

Instead, psychedelics hold the potential to guide individuals on journeys of self-discovery, healing, and personal growth. While substances like LSD may produce tolerance, they do not induce the compulsive drug-seeking behaviors characteristic of addictive substances. Examples of psychedelics include LSD (lysergic acid diethylamide), psilocybin (found in magic mushrooms), DMT (dimethyltryptamine), and mescaline (found in peyote cacti). Psychedelics, a term coined by British psychiatrist Humphry Osmond, encompass a broad category of substances known for their mind-altering effects.

How do psychedelic and dissociative drugs affect pregnancy?

The effects of psychedelic and dissociative drugs during pregnancy are not well understood, as data are limited. NIDA supports and conducts research to learn whether some of these drugs may help treat substance use disorders in medical settings. See NIDA-funded projects related to psychedelic and dissociative drugs, and learn more about related clinical trials. NIDA conducts and supports research on psychedelic and dissociative drugs to help inform health decisions and policies related to their use. Researchers are also investigating other drugs sometimes classified as psychedelic and dissociative drugs, such as MDMA, and the way they work in the brain. Research suggests that the most prominent psychedelic effects stem from activity in the brain’s prefrontal cortex, an area involved in mood, cognition, and perception.17,18 Psychedelic drugs also temporarily disrupt communication between different brain regions, including the regions collectively known as the default mode network (DMN).

A small laboratory study published on psilocybin, DMT, and mescaline suggested that these psychedelic drugs are “weakly reinforcing,” indicating their use is not likely to lead to a substance use disorder.67 However, some evidence suggests people may quickly develop a tolerance to psychedelic drugs, meaning they must keep taking more of the drug to experience the same level of effects.24 While short-term positive and negative mood changes are common with psychedelic and dissociative drugs, more research is needed to better understand the long-term effects these substances may have on mental health. Most people who report using psychedelic and dissociative drugs do so outside of medical or research settings.1,28 While further research is also needed to better understand the health and safety impacts of typical use of these drugs, some serious adverse effects and safety issues have been identified.14,27 While researchers debate how to describe and classify psychedelic and dissociative drugs and other drugs with similar properties, they generally group these drugs according to how they work in the brain.3 Some people use the term “hallucinogens” to refer to all or some psychedelic and dissociative drugs. Nutt’s findings underscored that psychedelic substances do not present the same level of physical risk or dependence potential as many legal and illegal drugs.

Treat addiction with psychedelics?

For an example of current techniques applied to enable our understanding of how psychedelics produce their effects, please see Singleton et al. (2021). When evaluating the potential risks of psychedelic medicines as scientifically and objectively as possible, it is important to acknowledge that some of the evidence presented above (particularly studies conducted pre-prohibition) is not of the highest standard as described by Rucker et al. (2016) in their recent review. The dose (Gable, 2004), route of administration and likelihood of any underlying health condition/s (Malleson, 1971) also determine potential adverse effects, such as multi-organ failure, hyperthermia and intoxication leading to other risky behaviours (Nichols and Grob, 2018; Van Amsterdam et al., 2011). Based on deaths registered in England and Wales (between 1993 and 2020), there were eight deaths where LSD was specified on the death certificate and two deaths where psilocybin was mentioned, with one death certificate reporting the presence of both substances.

Combined results from Riba and Barbanoj’s (2005) double-blind pilot study and clinical trial with ayahuasca found that 6 out of the 24 volunteers in their study met the diagnostic criteria for hypertension during drug administration and one volunteer had tachycardia. Other studies reported similar results for LSD (Dolder et al., 2016; Gasser et al., 2014; Holze et al., 2020, 2021), psilocybin (Carbonaro et al., 2018), ayahuasca (Dos Santos et al., 2012) and DMT (Strassman et al., 1996). Most studies examined involved healthy subjects, some included patients with anxiety, or OCD, and in one large study of participants in ayahuasca ceremonies, a small number were taking antidepressant medication. Psychedelics can induce short-lived and non-clinically significant sympathomimetic effects, including on heart rate, BP, pupil size and body temperature, as shown in Table 4. This is over 700 times the high dose of 25 mg used in clinical studies, for an average body weight of 70 kg.

“We want these molecules to be used in a medical way by qualified clinicians and therapists who understand these types of therapies and how they can work best.” “It’s a very powerful addiction interrupter.” Marks said there are efforts in some cities and states across the U.S. to decriminalize psilocybin. All of our panelists will also agree that these are not first-line treatments. We also know that a lot of the treatments that we have are not particularly effective,” said Tabashneck, senior fellow of law and applied neuroscience, a collaboration between the Center for Law, Brain & Behavior and the Petrie-Flom Center. Yet fewer than 10 percent get treatment, she said.

Among other health effects, dissociative drugs can also alter people’s perception of reality. While more research is needed, the reported incidence of serious adverse events from professionally supervised use of specific psychedelic and dissociative drugs, such as in clinical trials, is relatively ketamine toxicity statpearls ncbi bookshelf low.2,10,11,26 However, many past clinical studies on these drugs have not adequately assessed or reported on adverse events.27 Although research is ongoing, studies suggest psychedelic drugs—such as psilocybin, LSD, and DMT—primarily affect 5-HT2A receptors in the brain, which ordinarily are activated by the neurotransmitter (chemical messenger) serotonin.10 NIDA supports and conducts research on the short- and long-term health effects of psychedelic and dissociative drugs to better inform health decisions and policies related to their use. Psychedelic drugs (also called “classic psychedelics” or “psychedelics”), including psilocybin and LSD, mainly interact with specific receptors, which are molecular structures in the brain.

In Canada, last year, the Minister of Health gave approval on a case-by-case basis for several terminally ill patients to receive psilocybin for the purposes of treating end-of-life distress (Lozano, 2020). Going beyond decriminalisation, Oregon voters recently passed a bill giving the Oregon Health Authority 2 years to develop a division to regulate the production, distribution, administration and possession of psilocybin. We explore the evidence base for these adverse effects to elucidate which of these harms are based largely on anecdotes versus those that stand up to current scientific scrutiny.