Importantly, there were no sex differences, and increased age and experience with the drugs was related to slightly less intense effects. Recent clinical research also suggests that unpleasant reactions (such as anxiety, paranoia and confusion during the psychedelic experience) tend to be transient and do not diminish the therapeutic benefits of psychedelics in reducing depressive symptoms (Carhart-Harris et al., 2016). In their seminal comparative drug harms studies, using Multi-Criteria Decision Analysis (MCDA), Nutt et al. (2010) ranked LSD among the drugs with the lowest harms, both for the individual and to society and ‘magic mushrooms’ received the lowest overall harm score (Nutt et al., 2010). Looking at psilocybin, Gable (1993) concluded that it carries a lower dependence risk than caffeine, and being among the lowest risks of death of all major substance abuse categories. Psilocybin has been evaluated, together with LSD in various preclinical models of dependence and abuse potential, yielding qualitatively similar results, with no physical dependence or withdrawal (Martin, 1973). Today, research has repeatedly shown that psychedelics do not cause dependence or compulsive use (Halberstadt, 2015; Johnson et al., 2018; Morgenstern et al., 1994; Nichols, 2016).

Harms to self and other

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).

Adverse effects of psychedelics

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).

• These drugs may also help a person quit smoking or abstain from alcohol.
• Thus, HPPD symptoms could potentially be conceived as a form of trauma response, similar to PTSD, or a form of health anxiety evoked by residual symptoms of the original experience.
• These are part of the brain’s system for transporting glutamate, another neurotransmitter.
• A single use rarely triggers addiction, but regular use or mixing with substances like alcohol amplifies dependence, as highlighted by the Addiction Center.
• Microdosing refers to regularly taking these drugs in very small amounts, typically one tenth to one twentieth of a typical non-clinical dose.
• An adverse reaction to psychedelics can include a ‘bad trip’ (in lay language) or a ‘challenging experience’ (in therapeutic language).

Types of Psychedelic Drugs

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.

• While more research is needed, laboratory research and a few human studies suggest that using the dissociative drug ketamine outside of a clinical setting can lead to cravings as well as symptoms of withdrawal.68
• People have used hallucinogens for religious or healing rituals for many years.
• Compared to substances like alcohol and opioids, which have relatively low thresholds for toxicity, psychedelics are significantly less dangerous in terms of overdose risk.
• Some of the perceived harms of psychedelics – for example, that they lead to addiction and are neurotoxic – are largely refuted by research of the past decades.

Risks from dangerous behavior

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.”

Overdose toxicity

While these occurrences are uncommon compared with other psychoactive drugs – especially alcohol – they are widely reported in the media which contributes considerably to public perceptions of their risks. Set and setting – the expectations and personal experiences of the users as well as the external environment – are established elements of psychedelic research and recognised as having a major impact on users’ experience (Aday et al., 2021; Johnson et al., 2008). As emotional experiences can be intensified when under the influence of psychedelics, set and setting are crucial. In summary, although there have been isolated case reports of abuse (e.g. Modak et al., 2019), the characterisation of psychedelics as addictive is based on misinformation and misunderstanding. Yet, while Gable (2006) suggests that the dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal, Winstock et al. (2013) argue that the very desirable effect profile of smoked DMT indicates a high abuse liability which may be offset by a low urge to use more. This finding was further confirmed in a detailed review by Carroll (1990) who found that PCP is a highly effective reinforcer in animals, whereas LSD and other hallucinogens are not.

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.

Drug Science receives an unrestricted educational grant from a consortium of medical psychedelics companies. Some of the perceived harms of psychedelics – for example, that they lead to addiction and are neurotoxic – are largely refuted by research of the past decades. However, as pharma becomes involved in PAP drug discovery to develop new psychedelic molecules with improved drug delivery systems, absorption, distribution, metabolism and excretion (ADME) profiles and reduced potential for toxicity in vulnerable populations, the processes described by Shahid et al. (2020) may become a requirement. PAP drug development currently involves plant medicines that have been used safely by indigenous populations for thousands of years, by western populations over successive generations and currently in clinical trials for many psychiatric disorders in controlled situations. Shahid et al. (2020) provide an extensive description of this process from drug target selection to testing in animal models, Phase I to Phase IV clinical studies to post-marketing surveillance and risk management.

How Do Hallucinogens Affect the Brain?

“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.

Psychedelics and Addiction: What Research Reveals

However, some hallucinogenic drugs may lead to tolerance and some people report experiencing withdrawal effects is it bad to mix weed and alcohol 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

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.

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.

There are many other treatment modalities that are out there, from regular treatment to medication-assisted recovery to other holistic modalities that can help us live better lives.” Psilocybin and ibogaine are federally illegal in the U.S., with some exceptions for medical research. Mark Guckel had struggled with crack addiction since high school. Information provided by NIDA is not a substitute for professional medical care or legal consultation. People report that they microdose to lessen mental health symptoms such as depression and stress, improve productivity, and ease pain.

In recent years, psychedelics have made a remarkable resurgence, particularly in the realm of mental health and well-being. LSD use can lead to tolerance, which means people require more of the substance in order to achieve the same effects. Factors such as dosage, environment, and personality play a role in how psychedelics affect people. The effects of DMT are much shorter than those of other psychedelics, typically lasting only an hour. The following are some of the most commonly used psychedelic substances. While psychedelic therapy shows promise in the treatment of a number of mental health conditions, it is important to recognize that this research is still in the early stages.

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.